Quantification of Treg cells in peripheral blood and lymph nodes of dogs with multicentric lymphoma / Quantificação de células Treg no sangue periférico e linfonodos de cães com linfoma multicêntrico

Lymphoma is a malignant tumor characterized by cell proliferation of lymphoid origin and corresponds to 90% of all hematopoietic neoplasms of dogs. Regulatory T cells (Tregs) have been the target of many investigations in oncology due to their potential of down-regulating immune responses, as well as ensuring the maintenance of active mechanisms of tumor suppression. The aims of the present study were to compare the percentage of Tregs in peripheral blood between dogs with multicentric lymphoma and healthy animals, together with the percentage of Tregs in peripheral blood and lymph nodes of dogs with multicentric lymphoma. Twenty-six animals were enrolled in the study: 10 healthy dogs comprised the control group (CG) and 16 dogs with multicentric lymphoma comprised the Lymphoma Group (LG). We observed that dogs in the LG showed a significantly higher Tregs expression in peripheral blood compared to the CG. No significant difference was observed between Tregs expression in lymph nodes and peripheral blood of the LG, however. With these results, it is possible to conclude that multicentric lymphoma is a neoplasm with high Tregs expression, which poses this as a condition of interest when investigating treatments that can suppress Regulatory T cells.(AU)

O linfoma é uma neoplasia maligna caracterizada pela proliferação neoplásica de células originadas de tecido linfoide e corresponde a cerca de 90% das neoplasias hematopoiéticas em cães. Células T reguladoras (Tregs) têm sido alvo de diversas investigações na área da oncologia devido ao potencial de regulação negativa da resposta do sistema imune e à manutenção ativa do mecanismo de imunossupressão tumoral. O objetivo do presente estudo foi a comparação da porcentagem de Tregs no sangue periférico entre cães com linfoma multicêntrico e animais saudáveis e a porcentagem de Tregs no sangue periférico e nos linfonodos de cães com linfoma multicêntrico. Foram utilizados 26 animais: 10 cães saudáveis, como grupo controle (CG), e 16 cães com linfoma multicêntrico, como grupo linfoma (LG). Observou-se maior expressão de Tregs no sangue periférico de cães do LG em comparação ao CG. Entretanto, não foi observada diferença significativa entre as expressões de Treg nos linfonodos e no sangue periférico do LG. Com esses resultados, foi possível concluir que o linfoma multicêntrico apresenta alta expressão de Tregs, tornando-se condição interessante para o estudo de tratamentos capazes de suprimir as células T reguladoras.(AU)

Immunotherapy and gene therapy as novel treatments for cancer / Inmunoterapia y terapia génica como nuevos tratamientos contra el cáncer

Abstract The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma. Ipilimumab is an anti-CTLA-4 antibody which demonstrated good results when administered to patients with melanoma. Gene therapy has also shown promising results in clinical trials. Particularly, Herpes simplex virus (HSV)-mediated delivery of the HSV thymidine kinase (TK) gene to tumor cells in combination with ganciclovir (GCV) may provide an effective suicide gene therapy for destruction of glioblastomas, prostate tumors and other neoplasias by recruiting tumor-infiltrating lymphocytes into the tumor. The development of new treatment strategies or combination of available innovative therapies to improve cell cytotoxic T lymphocytes trafficking into the tumor mass and the production of inhibitory molecules blocking tumor tissue immune-tolerance are crucial to improve the efficacy of cancer therapy.

Resumen El sistema inmune interactúa íntimamente con los tumores durante el proceso del desarrollo de la enfermedad y su progresión a metástasis. Esta compleja comunicación entre el sistema inmune y las células tumorales puede prevenir o promover el crecimiento del tumor. Los nuevos enfoques terapéuticos que aprovechan los mecanismos inmunológicos, ya sea por el bloqueo de señales inhibitorias o por la activación directa de células efectoras, han mostrado resultados prometedores. El bloqueo de puntos de control inmunológicos (immune-checkpoints) con anticuerpos monoclonales dirigidos contra receptores que normalmente inhiben el sistema inmune, como CTLA-4 o PD-1, ha resultado ser un tratamiento exitoso para pacientes con melanoma avanzado. El fármaco ipilimumab es un anticuerpo anti-CTLA-4 que ha demostrado buenos resultados terapéuticos en pacientes con melanoma. Por otro lado, la terapia génica también ha mostrado resultados prometedores en ensayos clínicos. En especial, la administración de la enzima timidina quinasa del virus Herpes simplex (HSV-TK) en combinación con el fármaco ganciclovir (GCV) ha mostrado ser una terapia suicida muy efectiva para la destrucción de diferentes neoplasias incluyendo glioblastomas y tumores prostáticos, por un mecanismo que involucra el reclutamiento de linfocitos infiltrantes de tumor. Es importante la búsqueda de nuevas estrategias o la combinación de terapias innovadoras, con el fin de involucrar tanto la atracción de linfocitos citotóxicos así como el empleo de moléculas que inhiban la inmunotolerancia del tejido tumoral para mejorar la eficiencia de los tratamientos contra el cáncer.

Relationship between percentage of regulatory t-cells and dental amalgam fillings / Relación entre el porcentaje de células t-reguladoras y obturaciones de amalgama

Abstract: introduction: regulatory T-cells are the main component of peripheral tolerance and their level is decreased in autoimmunity. In dental amalgam, a mixture of metals is used as a restorative material. During daily a ctivities, these metals are ingested and affect renal, neurosensory and immune systems. Studies have demonstrated an increased risk of autoimmune diseases in patients with dental amalgam fillings. It was hypothesized that the percentage of regulatory T-cells decreases in individuals with amalgam fillings. Therefore this study was designed to determine and compare the percentage of regulatory T-cells in individuals with and without amalgam fillings. Material and Methods: This was a cross-sectional study. Subjects were divided into two groups with each group consisting of 40 individuals. Group I (study group) comprised individuals with amalgam fillings, and Group II (control group), individuals without amalgam fillings in their teeth. Blood samples of all the participants were collected and tagged with CD4 FITC, CD25 PE and CD127 PerCP-Cy monoclonal antibodies for the detection of regulatory T-cells, FACSCalibur was used for this purpose. Results: The percentage of regulatory T-cells in the control group was high (77.77 +/- 5.54 percent) compared to the study group (76.09 +/- 7.68 percent), however, on comparison, the difference was not statistically significant (p=0.25). Conclusion: Dental amalgam fillings did not show a declining effect on the percentage of regulatory T-cells.

Resumen: introducción: las células T reguladoras son el principal componente de la tolerancia periférica y su nivel se reduce en la autoinmunidad. En las obturaciones de amalgama, una mezcla de metales se utiliza como un material de restauración. Durante las actividades diarias, estos metales se ingieren y afectan el sistema renal, neurosensorial e inmunológico. Los estudios han demostrado un aumento del riesgo de enfermedades autoinmunes en pacientes con amalgamas dentales. Se planteó la hipótesis que el porcentaje de células T reguladoras disminuye en individuos con obturaciones de amalgama. Por tanto, este estudio fue diseñado para determinar y comparar el porcentaje de células T reguladoras en individuos con y sin obturaciones de amalgama. Material y Métodos: Se realizó un estudio de corte transversal. Los sujetos fueron divididos en dos grupos, cada uno con 40 individuos. El grupo I (de estudio) estuvo conformado por individuos con obturaciones de amalgama y el grupo II (de control) por individuos sin obturaciones de amalgma. Se colectaron muestras de sangre, las que fueron marcadas con anticuerpos monoclonales CD4 FITC, CD25 PE y CD127 PerCP-C para detectar las células T reguladoras, se utilizó FACSCalibur para este propósito. Resultados: El porcentaje de células T reguladoras en el grupo control fue alta (77,77 +/- 5,54 por ciento) en comparación con el grupo de estudio (76,09 +/- 7,68 por ciento), pero esta diferencia no fue estadísticamente significativa (p=0,25). Conclusión: Las obturaciones de amalgama no se asociaron con una disminución en el porcentaje de células T reguladoras.

Pathogenesis of thyroid autoimmune disease: the role of cellular mechanisms.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two very common organ-specific autoimmune diseases which are characterized by circulating antibodies and lymphocyte infiltration. Although humoral and cellular mechanisms have been classically considered separately in the pathogenesis of autoimmune thyroid diseases (AITD), recent research suggests a close reciprocal relationship between these two immune pathways. Several B- and T-cell activation pathways through antigen-presenting cells (APCs) and cytokine production lead to specific differentiation of T helper (Th) and T regulatory (Treg) cells. This review will focus on the cellular mechanisms involved in the pathogenesis of AITD. Specifically, it will provide reasons for discarding the traditional simplistic dichotomous view of the T helper type 1 and 2 pathways (Th1/Th2) and will focus on the role of the recently characterized T cells, Treg and Th17 lymphocytes, as well as B lymphocytes and APCs, especially dendritic cells (DCs).

Regulatory T cells in dogs with multicentric lymphoma: peripheral blood quantification at diagnosis and after initial stage chemotherapy / Células T reguladoras em cães com linfoma multicêntrico: quantificação, em sangue periférico, no momento do diagnóstico e após etapa inicial do tratamento quimioterápico

Lymphoma is the most common hematopoietic malignancy in dogs and one of the most frequent among all neoplastic diseases in this species. It can occur in several anatomical locations with distinct histological and immunophenotypes. Depending on the host immune response towards the tumor, prognosis information could be collected. Because its well established immunosuppressant, antitumor activity, the function of regulatory T cells (Tregs) in canine neoplasias has been investigated. In this study, we sought to quantify, using flow cytometry, the Tregs subpopulation in peripheral blood of healthy dogs (10) and in those diagnosed with type-B (14) and type-T (8) multicentric lymphoma before (at diagnosis) and after the first cycle (5-week) of 19-week Madison-Wisconsin (MW) protocol of chemotherapy. Our results indicated that dogs with lymphoma showed higher percentage of Tregs (18,84±2,56) when compared to healthy dogs (4,70±0,50) (P<0,01). In addition, 5-week chemotherapy treatment reduced the Tregs subpopulation (7,54±1,08) to levels similar to control (4,70±0,50) (P>0,05). There was no difference in Tregs percentage between B-type (17,45±2,77) and T-type (21,27±5,27) lymphoma (P>0,05). With this, we conclude that canine lymphoma increases Tregs in the peripheral blood and the MW protocol of chemotherapy reduces this cell subpopulation to control values.

O linfoma é a neoplasia hematopoiética mais comum nos cães e uma das mais frequentes, dentre todas as neoplasias, nesta espécie. Apresenta-se em diversas localizações anatômicas e pode apresentar classificações histológicas e imunofenotipos distintos. Dependendo da resposta imune do paciente frente à instalação de um tumor, algumas informações sobre o prognóstico podem ser obtidas. Atualmente, as células T reguladoras (Tregs) vêm sendo estudadas em algumas neoplasias caninas, por seu comprovado potencial imunossupressor, principalmente por inibir a resposta antitumoral. Neste contexto, o presente trabalho teve como objetivos quantificar, por citometria de fluxo, as células Tregs em sangue periférico de cães com linfoma multicêntrico de imunofenótipos B e T, respectivamente 14 e 8 cães, no momento do diagnóstico e após o primeiro ciclo de quimioterapia antineoplásica com o protocolo Madison-Wisconsin (MW) de 19 semanas adaptado, e comparar com cães saudáveis (n=10), buscando quantificá-las em cães com linfoma de diferentes imunofenótipos antes e após a 5ª semana do protocolo MW. Os resultados mostraram que cães com linfoma apresentaram uma porcentagem significativamente maior de Tregs (18,84±2,56) quando comparada aos cães sem neoplasia (4,70±0,50) (P<0,01). Além disso, após a quinta semana de tratamento houve uma significante redução da população de Tregs (7,54±1,08), atingindo valores semelhantes a dos cães controle (4,70±0,50) (P>0,05). Não houve diferença nas Tregs em relação aos imunofenotipos B (17,45±2,77) e T (21,27±5,27) (P>0,05). Concluiu-se que o linfoma em cães leva a um aumento de células Tregs e que o tratamento com o protocolo quimioterápico MW reduz significativamente as células Tregs em sangue periférico, atingindo valores próximos aos dos cães saudáveis.

The role of Th17 and regulatory T cells (TREGs) in immunomodulation of experimental periapical lesions / Papel das células Th17 e T reguladoras (TREGs) na imunomodulação de lesões periapicais experimentais

A patogênese das lesões periapicais é determinada pelo equilíbrio entre a resposta imune pró-inflamatória do hospedeiro e a resposta anti-inflamatória/reparo. Diferentes subtipos de linfócitos e seus produtos têm sido implicados na patogênese dessas lesões, tais como as células T reguladoras (Tregs) e Th17. Enquanto as Tregs parecem ser potenciais agentes imuno-reguladores, Th17 parece estar associada à maior severidade da doença. Neste estudo, foram investigados o envolvimento de Tregs e Th17, além do impacto de diferentes terapias na progressão de lesões periapicais experimentais. Para isso, lesões periapicais foram induzidas (exposição pulpar e inoculação bacteriana) em camundongos C57BL/6, IL- 17KO e CCR4KO tratados com anticorpos anti-GITR (inibe a função de Treg) ou com CCL22p, partículas de ácido poliláctico-glicólico (induz a migração de Tregs). Além disso, os camundongos WT foram tratados com anti-RANKL utilizando protocolos contínuos ou intermitentes, ou com anti-TNF como controle. Posteriormente, analisou-se o fluxo e fenótipo de Tregs e Th17, perda óssea periapical e expressão de citocinas inflamatórias/imunológicas e marcadores de reparo (RealTimePCRarray, ELISA). A inibição de Tregs (depleção de CCR4 ou terapia anti-GITR), aumentou significantemente a severidade da lesão, associada com o aumento da expressão de citocinas pró-inflamatórias, Th1, Th17 e mediadores de destruição tecidual em paralelo com a diminuição dos marcadores de Treg e de reparo. A liberação local de CCL22 no canal radicular resultou na migração de Treg, dependente de CCR4, levando à modulação da lesão periapical, associada com a diminuição da expressão de marcadores pró-inflamatórios e de destruição tecidual em paralelo com o aumento dos marcadores de Tregs e de reparo. O tratamento anti-RANKL impediu o desenvolvimento da lesão, mas provocou uma resposta inflamatória contínua caracterizada pela elevada expressão de citocinas pró-inflamatórias e mediadores de destruição tecidual e diminuição da expressão dos marcadores de Tregs e de reparo. Este tratamento levou à recidiva da lesão e foi associado com o aumento da razão células TCD4 efetoras/supressoras e com o perfil de expressão gênica de lesões ativas. O tratamento anti-TNF limitou a progressão das lesões e não promoveu sua recidiva após o término da terapia, estando associado à resposta do hospedeiro atenuada. Por fim, a ausência de IL-17 resultou em lesões menos severas, associadas com o aumento da expressão de marcadores de reparo e citocinas anti-inflamatórias, em paralelo com a menor expressão de marcadores de destruição tecidual e citocinas pró-inflamatórias. De fato, observou-se menor concentração de osteoclastos, neutrófilos e células inflamatórias, na ausência de IL-17. Conclui-se, portanto, que as células T reguladoras são essenciais no controle da lesão periapical, enquanto as células Th17 acentuam a severidade dessas lesões. Comparando com outras estratégias clínicas, tais como a terapia anti-RANKL que perpetua a resposta inflamatória do hospedeiro levando a recidiva da lesão, a quimioatração de Treg bem como a inibição de Th17 podem ser estratégias promissoras para o manejo clínico das lesões periapicais.(AU)

The pathogenesis of periapical lesions is determined by the balance between host proinflammatory immune response and counteracting anti-inflammatory and reparative responses. In this context, different subtypes of lymphocytes and their products have been implicated in periapical lesion pathogenesis, such as regulatory T cells (Tregs) and Th17. While Tregs has been demonstrated as potential immunoregulatory agents, Th17 has been correlated with greater severity of disease. In this study, we investigated (in a cause-and-effect manner) the involvement of Tregs and Th17, besides the impact of different therapies in the progression of experimental periapical lesions. With this aim, periapical lesions were induced (pulp exposure and bacterial inoculation) in C57Bl/6 (wild-type), IL-17KO and CCR4KO mice and treated with anti­glucocorticoid-induced TNF receptor family regulated gene (anti-GITR) to inhibit Treg function or alternatively with CCL22-releasing, poly lactic-glycolic acid particles to induce site-specific migration of Tregs. Furthermore, WT mice were treated with anti-RANKL using continuous or intermittent protocols, and with anti-TNF therapy as a control. After treatment, lesions were analyzed for Treg or Th17 influx and phenotype, overall periapical bone loss, and inflammatory/immunologic and wound healing marker expression (RealTimePCRarray, ELISA). Treg inhibition by anti-GITR or CCR4 depletion results in a significant increase in periapical lesion severity, associated with upregulation of proinflammatory, Th1, Th17, and tissue destruction markers in parallel with decreased Treg and healing marker expression. The local release of CCL22 in the root canal system resulted in the promotion of Treg migration in a CCR4-dependent manner, leading to the arrest of periapical lesion progression, associated with down regulation of proinflammatory and tissue destruction markers in parallel with increased Treg and healing marker expression. Anti-RANKL treatment arrested lesion development, but prompted a continuous inflammatory response characterized by unremitting elevated expression of proinflammatory cytokines and tissue destructive mediators, and decreased expression of Tregs and wound healing markers levels. This treatment triggered lesion development relapse and was associated with high TCD4 effector/suppressor cells ratio and active lesions gene expression signature. Anti-TNF treatment limits lesions progression and does not drives lesions relapse upon cessation, being associated with attenuated host response. Finally, the absence of IL-17 results in a significant decrease in periapical lesions severity, associated with upregulation of healing markers and antiinflammatory cytokines, in parallel with decreased expression of tissue destruction markers and proinflammatory cytokines. Indeed, histomorphometric analysis showed lower concentration of osteoclasts, neutrophils and mononuclear cells in periapical lesions without IL-17. Therefore, we concluded that regulatory T cells are essential in the control of apical periodontitis, while Th17 cells accentuate the lesions severity. Compared with other clinical strategies, such as anti-RANKL therapy, which perpetuates the host inflammatory response prompting lesion relapse, chemoattraction of Treg as well as inhibition of Th17 may be promising strategies for the clinical management of periapical lesions.(AU)

Inducción de células T reguladoras por estatinas: alternativa terapéutica para el control del asma extrínseca / Induction of regulatory T cells by statins: alternative therapy for the control of extrinsic asthma

El asma bronquial extrínseca se origina por una reacción inmunológica de hipersensibilidad tipo I, desencadenada principalmente por alérgenos ambientales. Clásicamente, la respuesta inmune mediada por células T CD4+ con perfil Th2 determina las principales características de esta enfermedad, con la infiltración de eosinófilos y basófilos que median la inflamación crónica de las vías aéreas. Se ha observado que las células T reguladoras pueden actuar como moduladores endógenos durante los procesos asmáticos, controlando la exacerbación de las crisis y disminuyendo el daño tisular. Aunque los glucocorticoides son el principal tratamiento para el asma, solo alivian temporalmente los síntomas y se asocian con efectos adversos y aparición de resistencia, lo cual ha incentivado el desarrollo de alternativas terapéuticas que modulen la respuesta inmune y controlen la inflamación crónica. Recientemente, se ha postulado que las estatinas podrían ser una alternativa promisoria para disminuir la respuesta inflamatoria y disminuir la morbilidad asociada a esta enfermedad, debido a su gran potencial inmunomodulador, entre los que se destaca la inducción de células T reguladoras(AU)

Extrinsic asthma is caused by an immunological type I hypersensitivity reaction triggered mainly by environmental allergens. Usually, immune response mediated mainly by CD4 + T cells with Th2 profile determines the main features of extrinsic asthma, including infiltration of eosinophils and basophils that mediate chronic inflammation of the airways. It has been observed that regulatory T cells may act as endogenous modulators during asthmatic processes, controlling crisis exacerbation and decreasing tissue damage. Although glucocorticoids are the main treatment for asthma, these only relieve symptoms temporarily and are associated with adverse effects and development of resistance, which has encouraged the development of alternative therapies that modulate the immune response and control chronic inflammation. Recently, it has been postulated that statins may be a promising alternative to reduce the inflammatory response and decrease the morbidity associated with this disease, due to its great immunomodulator potential, especially in the induction of regulatory T cells(AU)

Tolerancia inmunológica, un recorrido en el tiempo: cómo discriminar entre lo propio y lo extraño / Immune tolerance, a walk through time: How does the immune system differentiate between self and foreign

Resumen Desde los primeros estudios en inmunología, ha sido evidente la necesidad de entender cómo, en condiciones normales, el sistema inmune tolera los antígenos propios y ataca algunos antígenos extraños que percibe como potencialmente peligrosos, y cómo, bajo ciertas circunstancias, la pérdida de la tolerancia desencadena enfermedades autoinmunes. Ha pasado más de medio siglo desde que Billingham, Medawar y Brent demostraron en un modelo experimental algunos eventos involucrados en el desarrollo de la tolerancia inmunológica. Desde entonces, los inmunólogos de trasplante han centrado sus esfuerzos en dilucidar los mecanismos que conllevan al mantenimiento de la tolerancia, con la esperanza de eludir las complicaciones de la inmunosupresión no específica y conseguir la prevención del rechazo crónico. Medawar (1953) argumentaba que durante el trasplante el sistema inmune del individuo se hacía tolerante al tejido trasplantado, manteniéndose la respuesta a otros antígenos. Estudios recientes han demostrado que la pérdida de la tolerancia al trasplante está asociada con una hiperrespuesta a los antígenos del tejido trasplantado, hecho que ha atormentado a los inmunólogos clínicos, quienes han encaminado sus esfuerzos a desarrollar sistemas de medición precisos que les permita evaluar qué tan tolerante podría ser un individuo al trasplante. Los intentos por inducir tolerancia en el individuo, se basan en la comprensión de los mecanismos básicos de tolerancia, cuyo conocimiento se ha desarrollado paralelamente con una mejor apreciación de la complejidad de la tolerancia inmune. En particular, se ha avanzado mucho en la comprensión del papel esencial de las células dendríticas tolerogénicas (CDT) y del mantenimiento de la tolerancia por células T reguladoras.

Abstract Since the first studies in immunology, there has been a clear need to understand how, under normal conditions, the immune system tolerates its own antigens and attacks some foreign antigens that it perceives as potentially dangerous and how, in certain circumstances, the loss of tolerance triggers autoimmune diseases. It has been over half a century since Billingham, Brent and Medawar demonstrated, in an experimental model, the mechanisms involved in the development of immunological tolerance. Since then transplant immunologists have intensively investigated the mechanisms involved in maintaining tolerance, in the hope of avoiding the complications of non-specific immunosuppression, as well as the prevention of chronic rejection. An important characteristic was observed by Medawar, who argued that during transplantation an individual's immune system is tolerant to transplanted tissue, maintaining the response to other antigens. Recent studies have shown that loss of tolerance to transplantation is associated with a hyper-response to antigens of the transplanted tissue; a problem that has plagued clinical immunologists, who have focused their efforts on developing accurate measurement systems to enable them to measure how an individual could be tolerant to transplant. Attempts to induce tolerance in the individual are based on understanding the basic mechanisms of tolerance, in which there has been significant progress. This growth in knowledge has been in parallel with a better appreciation of the complexity of immune tolerance. In particular, progress has been made in understanding the essential role of tolerogenic dendritic cells (CDS) and the maintenance of tolerance by regulatory T cells.

Participación de los linfocitos T reguladores en el cáncer de ovario / Involvement of regulatory T cells in ovarian cancer

Los linfocitos T Reguladores (Treg) son una subpoblación de células linfoides cuya función es la regulación del sistema inmune. Estas células tienen funciones supresoras que intervienen en la evolución y control de los tumores malignos. En el cáncer de ovario se ha evidenciado un incremento de las Treg en microambiente del tumor y en circulación sistémica. El objetivo de este trabajo es actualizar los conocimientos relacionados con la participación del sistema inmune en el cáncer de ovario. Se empleó la revisión documental, a través de buscadores de información disponibles en Hinari. El incremento de los linfocitos Treg, en el microambiente del tumor y a nivel sistémico, constituye uno de los mecanismos que le permiten al tumor evadir la respuesta inmune. Este mecanismo no tiene la misma repercusión en todos los tumores, sin embargo, en el cáncer de ovario su existencia sí determina el avance de la enfermedad. Las Treg inhiben a las células efectoras por mecanismos dependientes del contacto célula-célula y por la liberación de citoquinas como la interleucina 10 y factor transformador del crecimiento beta. El resultado de este incremento es que contribuye a desencadenar los mecanismos de tolerancia a la acción del sistema inmune, asociándose por ende a parámetros de mal pronóstico. Existen evidencias científicas sobre la participación de los linfocitos Treg en el cáncer de ovario, que han permitido comprender la repercusión que ejercen en las manifestaciones clínicas y pronóstico de esta enfermedad, proponiendo nuevos y atractivos blancos terapéuticos que mejorarán el curso de esta(AU)

Regulatory T cells (Treg) lymphocytes are a subpopulation of lymphoid cells whose function is the regulation of the immune system. These cells have suppressor functions involved in the development and monitoring of malignancies. In ovarian cancer, an increase of Treg in tumor microenvironment and systemic circulation has been shown. The objective of this paper is to update the knowledge related to immune system involvement in ovarian cancer. Document review was used, through information search engines available on Hinari. The increase of Treg lymphocytes in the tumor microenvironment and systemic level is one of the mechanisms allowing the tumor to evade the immune response. This mechanism does not have the same impact in all tumors, however, ovarian cancer itself determines the existence of the disease progress. The Treg cells inhibit effector cells by mechanisms dependent on cell-cell contact and the release of cytokines such as interleukin-10 and beta transforming growth factor. The result of this increase is helping to trigger the tolerance mechanisms to the immune system action, thereby associating with poor prognostic parameters. There is scientific evidence on the involvement of Treg lymphocytes in ovarian cancer, which have allowed the understanding the impact they have on this disease clinical features and prognosis, offering attractive new therapeutic targets that will improve this disease course(AU)

Participación de los linfocitos T reguladores en el cáncer de ovario / Involvement of regulatory T cells in ovarian cancer

Los linfocitos T Reguladores (Treg) son una subpoblación de células linfoides cuya función es la regulación del sistema inmune. Estas células tienen funciones supresoras que intervienen en la evolución y control de los tumores malignos. En el cáncer de ovario se ha evidenciado un incremento de las Treg en microambiente del tumor y en circulación sistémica. El objetivo de este trabajo es actualizar los conocimientos relacionados con la participación del sistema inmune en el cáncer de ovario. Se empleó la revisión documental, a través de buscadores de información disponibles en Hinari. El incremento de los linfocitos Treg, en el microambiente del tumor y a nivel sistémico, constituye uno de los mecanismos que le permiten al tumor evadir la respuesta inmune. Este mecanismo no tiene la misma repercusión en todos los tumores, sin embargo, en el cáncer de ovario su existencia sí determina el avance de la enfermedad. Las Treg inhiben a las células efectoras por mecanismos dependientes del contacto célula-célula y por la liberación de citoquinas como la interleucina 10 y factor transformador del crecimiento beta. El resultado de este incremento es que contribuye a desencadenar los mecanismos de tolerancia a la acción del sistema inmune, asociándose por ende a parámetros de mal pronóstico. Existen evidencias científicas sobre la participación de los linfocitos Treg en el cáncer de ovario, que han permitido comprender la repercusión que ejercen en las manifestaciones clínicas y pronóstico de esta enfermedad, proponiendo nuevos y atractivos blancos terapéuticos que mejorarán el curso de esta

Regulatory T cells (Treg) lymphocytes are a subpopulation of lymphoid cells whose function is the regulation of the immune system. These cells have suppressor functions involved in the development and monitoring of malignancies. In ovarian cancer, an increase of Treg in tumor microenvironment and systemic circulation has been shown. The objective of this paper is to update the knowledge related to immune system involvement in ovarian cancer. Document review was used, through information search engines available on Hinari. The increase of Treg lymphocytes in the tumor microenvironment and systemic level is one of the mechanisms allowing the tumor to evade the immune response. This mechanism does not have the same impact in all tumors, however, ovarian cancer itself determines the existence of the disease progress. The Treg cells inhibit effector cells by mechanisms dependent on cell-cell contact and the release of cytokines such as interleukin-10 and beta transforming growth factor. The result of this increase is helping to trigger the tolerance mechanisms to the immune system action, thereby associating with poor prognostic parameters. There is scientific evidence on the involvement of Treg lymphocytes in ovarian cancer, which have allowed the understanding the impact they have on this disease clinical features and prognosis, offering attractive new therapeutic targets that will improve this disease course

Las células T reguladoras en la enfermedad pulmonar obstructiva crónica / Regulatory T cells in chronic obstructive pulmonary disease

La exposición al humo del tabaco induce inflamación de las vías aéreas y es el principal factor de riesgo para desarrollar la enfermedad pulmonar obstructiva crónica (EPOC). En este proceso inflamatorio participan varias poblaciones celulares. Algunas fallas en la modulación de la respuesta inflamatoria han sido aceptadas como un factor para el desarrollo de esta enfermedad. Las células T reguladoras (Treg) son un tipo de linfocitos T CD4+ que modulan la respuesta inmune mediante contacto directo con las células efectoras, así como por la secreción de citocinas inmunorreguladoras. El papel de las células Treg en la EPOC no se encuentra completamente comprendido, por lo cual es importante evaluar su participación en la inmunopatogénesis de la enfermedad. Con el objetivo de elaborar una revisión sistemática de artículos originales que nos permitiera describir las células Treg (su origen, características y mecanismos de acción) y su participación en la EPOC, realizamos una búsqueda intencionada en las siguientes bases electrónicas: MEDLINE, AMED, PubMed y Scielo; para ello usamos la combinación de las siguientes palabras clave: <

Exposition to tobacco smoke has been established as the main risk factor to develop chronic obstructive pulmonary disease (COPD), by inducing inflammation of the airways. Several cell populations participate in this inflammatory process. It has been accepted that a maladaptive modulation of inflammatory responses plays a critical role in the development of the disease. Regulatory T cells (Treg) are a subset of T CD4+ lymphocytes that modulate the immune response through secretion of cytokines. The role of the Treg cells in chronic obstructive pulmonary disease is not clearly known, that is why it is important to focus in understanding their participation in the pathogenesis of the disease. To elaborate a systematic review of original articles in which we could describe Treg cells (their ontogeny, mechanisms of action) and their role in COPD, we made a systematic literature search in some data bases (MEDLINE, AMED, PubMed and Scielo) looking through the next keywords: ''COPD and Regulatory T cells/EPOC y células T reguladoras'', <

Análise do envolvimento do receptor de quimiocinas - CCR5 - na migração de células T reguladoras: correlação com o desenvolvimento de carcinoma espinocelular / Analysis of the involvement of CCR in the migration of T regulatory cells: the correlation with the development of squamous cell carcinoma

Apesar dos avanços sobre a efetiva participação das células T reguladoras (Treg) na resposta imune antitumoral, ainda existem vários pontos que precisam ser esclarecidos. Visto que, os fatores que controlam a migração destas células para o microambiente tumoral ainda não estão totalmente definidos, o esclarecimento dos mecanismos de migração de células Treg no contexto do câncer poderia fornecer novos alvos para o desenvolvimento de terapias mais específicas. Diversos modelos de estudo demonstraram que o recrutamento preferencial de células Treg ao invés de outros tipos de células T pode ser explicado pela expressão diferencial de receptores de quimiocinas como o CCR5. Assim, é de extrema importância estabelecer qual é o papel de CCR5 na migração de células Treg em tumores induzidos quimicamente e seu envolvimento no desenvolvimento tumoral. Baseado no exposto, o presente estudo analisou o envolvimento de CCR5 na migração de células Treg e a sua correlação com o desenvolvimento de carcinoma espinocelular (CEC) induzido quimicamente. Os resultados obtidos demonstraram que camundongos geneticamente deficentes de CCR5 (CCR5KO) apresentaram baixo número de células Treg nas lesões e foram menos suscetíveis ao desenvolvimento de carcinoma espinocelular. Na fase de progressão tumoral verificou-se o desenvolvimento de CEC in situ por animais CCR5KO em combinação com a maior infiltração leucocitária, enquanto camundongos do grupo controle (WTCEC) apresentaram lesões de CEC bem diferenciado associado à elevada frequência de células Treg no microambiente tumoral e menor infiltração leucocitária. Interessantemente, a transferência adotiva de células Treg CCR5+ para animais CCR5KO (CCR5CEC Treg) resultou no acúmulo destas células no microambiente tumoral, elevado nível de CCL4, CCL17 e CCL22, e aumento da suscetibilidade desses animais à carcinogênese química. Verificou-se o desenvolvimento de CEC indiferenciado por animais CCR5CEC Treg e este foi...

Considering the advances on the effective participation of regulatory T cells (Treg) in the antitumor immune response, there are still several points that need to be clarified. The mechanisms that control the Treg cells migration to the tumor microenvironment are not completely defined, for these reason, establish these mechanisms could provide new targets for the development of more specific therapies. Several study models have demonstrated that preferential recruitment of Treg cells rather than other types of T cells can be explained by the differential expression of chemokine receptors such as CCR5. Thus, the present study examined the involvement of CCR5 in the migration of Treg cells and their correlation with the development of squamous cell carcinoma (SCC) chemically induced. The results showed that CCR5 knockout mice (CCR5KO) showed a low number of Treg cells in the lesions and these animals were less susceptible to the development of squamous cell carcinoma. SCC in situ was developed in CCR5KO mice and associated with high leukocytes infiltration, whereas the development SCC well differentiated in the control group (WTSCC) was associated with a high number of Treg cells and lower leukocyte infiltration in the tumor microenvironment. Interestingly, adoptive transfer of CCR5+Treg cells to CCR5KO mice (CCR5SCC Treg) resulted in the accumulation of these cells, high levels of CCL4, CCL17 and CCL22 in the tumor microenvironment and increased susceptibility to chemical carcinogenesis. CCR5SCCTreg mice developed SCC undifferentiated associated with a higher incidence of macrophages, myeloid and dendritic cells, CD19+, CD4+ T, CD8+ T lymphocytes, and Treg cells in the stage of tumor progression. Another relevant aspect of our study was the observation that adoptive transfer of CD4+CD25-CCR5+ T cells to CCR5KO animals (CCR5SCC CD4+) induced the development of SCC moderately differentiated with intermediate features observed in the WTSCC and CCR5SCC Treg...

Participación de la prolactina en la respuesta inmune / Role of prolactin in the immune response

Existen evidencias de la relación entre el sistema inmune y el endocrino vía múltiples factores de comunicación, como citocinas, neuropéptidos, neurotransmisores y hormonas. Se ha demostrado la participación de la hormona prolactina en la respuesta inmune innata y adaptativa. Además de ser producida por la glándula pituitaria, también es producida y secretada por las células del sistema inmunológico. El objetivo de esta revisión fue puntualizar acerca de la participación de la prolactina secretada por estas células en la respuesta inmune.

Evidence exists about the relationship between the immune and the endocrine systems through communication of multiple factors such as cytokines, neuropeptides, neurotransmitters and hormones. Among the hormones, prolactin (PRL) has been shown to participate in the innate and adaptive immune response. In addition to being produced by the pituitary gland, PRL is also produced and secreted by cells of the immune system. The aim of this review is to update information about the involvement of PRL secreted by immune system cells in the immune response.

Análise do envolvimento de células T reguladoras na hanseníase / Analysis of the involvement of regulatory T cells in leprosy

A hanseníase é uma doença crônica causada por Mycobacterium leprae e apresenta diversas formas clínicas. O entendimento da interação parasita-hospedeiro na hanseníase evidenciou que ocorre a persistência assintomática do patógeno, caracterizando um estado de latência. Os fatores mais importantes relacionados com a permanência do patógeno são: a patogenicidade do agente infeccioso e o perfil da resposta imune, no qual os eventos de migração celular, produção de citocinas, as células efetoras e reguladoras são extremamente relevantes. As células T reguladoras (Treg) desempenham papel central na regulação da resposta imune em infecções crônicas o que favorece a persistência do patógeno. A importância de células T reguladores na hanseníase ainda é pouco conhecida. Neste trabalho investigou-se a presença de células T reguladoras em lesões e sangue periférico de indivíduos com hanseníase. Inicialmente avaliou-se a proliferação e a produção de citocinas por células mononucleares do sangue periférico (PBMC) de pacientes com hanseníase. Os resultados evidenciaram que não há diferenças quanto à proliferação de células T e produção de IFN-γ e TNF-α por células desses pacientes, mas a produção de IL-4 e IL-5 foi detectada apenas entre os pacientes com hanseníase virchoviana. Em relação à presença de células T reguladoras, os resultados evidenciaram aumento no número de linfócitos T CD4+CD25+FoxP3+ no sangue periférico de pacientes com hanseníase virchoviana. As células T reguladoras dos pacientes com hanseníase apresentaram elevada expressão de moléculas co-inibitórias PD-1, CTLA-4, GITR e ICOS. De modo relevante, as células T CD4+CD25+ isolados de pacientes com hanseníase virchoviana apresentaram maior atividade supressora quando comparado às células isoladas de pacientes com hanseníase tuberculóide. As células T CD4+CD25+ de pacientes com hanseníase virchoviana inibiram a proliferação de PBMC alogênico e a produção de IFN-γ e TNF-α...

Leprosy is caused by Mycobacterium leprae and its clinical features depend on the host immune background. The understanding of parasite-host interactions in leprosy have highlighted asymptomatic persistence of the pathogen, which indicates that this infection becomes latent. The most important factors related to the permanence of pathogens are: the pathogenicity of the infectious agents; the profile of the immune response developed by the host whose events of cellular migration, cytokines production, and the effector and regulatory cells are extremely relevant. The regulatory T cells (Treg) seem to play a central role in the regulation of the immune response in chronic infections, which favors the persistence of the pathogen. Herein, we analyzed the relation between tuberculoid and lepromatous leprosy with the presence and function of T regulatory cells from peripheral blood mononuclear cells (PBMC) and skin lesions from these patients. First, the proliferation and cytokine production of PBMC isolated from leprosy patients were analyzed. We did not observe any difference in the proliferation ability or IFN-γ and TNF-α release; however, the production of IL-4 and IL-5 was detected only in patients with lepromatous leprosy. Furthermore, T CD4+CD25+FoxP3+ cells were detected in the PBMC of patients with leprosy and these cells from lepromatous patients showed high expression of co-inhibitory molecules such as PD-1, GITR, CTLA-4 and ICOS. T CD4+CD25+cells isolated from patients with lepromatous leprosy were significantly more suppressive than the cells obtained from tuberculoid patients. In addition, TCD4+CD25+ cells isolated from patients with lepromatous leprosy inhibited allogeneic PBMC proliferation and their production of IFN-γ and TNF-α. The results also demonstrated that IL- 10 and TGF-ß were co-expressed with CD25+ cells at the inflammatory infiltrate of skin lesions from lepromatous patients, but similar results were not detected among tuberculoid...

La otra cara de Janus y la enfermedad tiroidea autoinmune

La enfermedad tiroidea autoinmune es una de las patologías más comunes dentro de la endocrinología. Este grupo de enfermedades que afectan la función tiroidea se consideran actualmente como parte de un espectro, donde por un lado se evidencia una hipofunción y donde predomina una respuesta inmune Th1 (Tiroiditis de Hashimoto) y en el lado opuesto, el de la hiperfunción, predomina una respuesta Th2 (Enfermedad de Graves). Si bien ambas enfermedades tienen ciertos locus de predisposición genética en común, las manifestaciones clínicas y el pronóstico de estas enfermedades son totalmente opuestas. Aunque se han planteado diversas teorías para explicar las diferencias en el patrón autoinmune de ambos extremos de este espectro, éstas no han logrado ilustrar la amplia variedad de fenotipos de esta patología. Evidencia actual sugiere que un grupo celular encargado de controlar la actividad de los elementos efectores de la respuesta inmune, limitando el daño hacia los tejidos del hospedador mediando la autotolerancia, y conocido como células T reguladoras, juegan un papel protagónico en el desarrollo de las enfermedades autoinmunes. El propósito de ésta revisión es exponer como la disregulación de la cara reguladora del sistema inmune, expresada tanto en la alteración de la función como en la expansión de las células T reguladoras, constituyen una piedra angular en las diversas formas de manifestación de la enfermedad tiroidea autoinmune.

Autoimmune thyroid disease is one of the most common diseases inside the field of endocrinology. This group of diseases affect the thyroid function in a manner that is now considered like a spectrum, where on one side there is evidence of hypofunction and a predominating Th1 response (Hashimoto´s thyroiditis), and on the opposite side, hyperfunction and a predominating Th2 response (Graves´ disease). Even though both diseases share loci for genetic predisposition, the outcome of each of them is totally opposite. Several theories have been proposed to explain the differences in the autoimmune patterns, but haven’t been able to explain the ample phenotypical manifestations of the disease. Current evidence suggests that a recently describe cellular group is in charge of controlling the effector elements of the immune response, limiting tissue damage and enhancing self-tolerance, these are the T regulator cells (Treg), which play a principal role in the development of autoimmune diseases. The purpose of this review is to expose the dysregulation of the regulatory side of the immune system expressed as the alteration of the functioning of Treg, which are now believed to be fundamental in the many phenotypes of autoimmune thyroid diseases.

Linfoma cutáneo de células T Revisión del tema con énfasis en la inmunopatogénesis / Cutaneous T-cell lymphoma: Review with emphasis on immunophatogenesis

Bajo el término linfoma cutáneo de células T (LCCT) se agrupa una serie de enfermedades que tienen en común la presencia de un clon maligno de células T y la afectación de la piel. La micosis fungoide (MF) es la forma más común de LCCT, seguida por el síndrome de Sèzary (SS). La causa definitiva de la MF es desconocida. El inmunofenotipo de la mayoría de los casos de MF es de células T de memoria CD3+CD4+CD45RO+CLA+CD8-. Los linfocitos T CD4+ malignos migran hasta la epidermis y se localizan alrededor de las células de Langerhans (LC). En el SS las células pierden el epidermotropismo e infiltran extensamente la dermis, la sangre y otros tejidos; estas células presentan un inmunofenotipo predominante de células T neoplásicas CD3+CD4+CD8-CD7-CD26- CD158k+CD94-. El perfil Th2 y la supresión de respuestas Th1 son dos factores críticos en la progresión de la enfermedad. Se han evaluado muy poco las alteraciones en la regulación inmune en el LCCT. Un mejor entendimiento de la función de las células T y de la inmunobiología de los LCCT permitiría mejorar el pronóstico, el tratamiento y el seguimiento de los pacientes con estas neoplasias.

The term cutaneous T-cell lymphoma (CTCL) refers to several diseases that have in common the presence of a malignant T-cell clone with involvement of the skin. Mycosis fungoides (MF) is the most common form of CTCL, followed by the Sèzary syndrome (SS). The cause of mycosis fungoides is unknown. Immunophenotype of most cases of MF is made up by memory T cells CD3+CD4+CD45RO+CLA+CD8-. Malignant T CD4+ lymphocytes migrate to the epidermis and localize around Langerhans cells. In SS, cells loose their epidermotropism and extensively infiltrate the dermis, blood and other tissues. These cells present a predominant immunophenotype of neoplasic T cells CD3+CD4+CD8-CD7-CD26-CD158k+CD94-. The Th2 profile and the supression of Th1 responses are two critical factors in the progression of the disease. Alterations in the immune regulation in CTCL have not been thoroughly evaluated. A better understanding of T-cell function and of the immunobiology of CTCL would allow to improve the prognosis, therapy and follow-up of patients with these neoplasias.

La tolerancia inmunológica a 50 años del premio nobel en medicina y fisiología: una perspectiva como mecanismo de respuesta inmune frente a patógenos: [revisión] / Immune tolerance at 50 years from the nobel prize in medicine and physiology: a perspective as a mechanism of immune response against pathogens: [review]

El sistema inmune es responsable de proteger al organismo contra agentes extraños mediante el desarrollo de un repertorio de receptores, capaces de reconocer antígenos de toda etiología, diferenciando moléculas propias de extrañas, estableciendo además fundamentos para la identidad biológica del individuo. Para ello dispone de una red compleja de mecanismos celulares y moleculares que son los responsables de la llamada tolerancia inmune. La regulación de la interacción entre el sistema inmune y los antígenos que eventualmente puede conducir al desarrollo de tolerancia, es crítica tanto en condiciones fisiológicas como en diferentes estados de patología. Desde las primeras descripciones de Medawar, las cuales mostraron que el fenómeno de tolerancia es adquirido y central para la homeóstasis del sistema inmune, un número importante de mecanismos se han propuesto para explicar la tolerancia inmune. Sin embargo, un mecanismo único de autotolerancia ha surgido: la generación de linfocitos T reguladores antígeno específicos, también conocidos como células T reguladoras (Treg), de origen central o periférico. Esta subpoblación de linfocitos con funciones supresoras ha mostrado un papel muy importante no solo en el control de enfermedades autoinmunes, sino además en la inmunopatogenia de enfermedades infecciosas crónicas, ya sean inducidas por el patógeno como mecanismo de escape o por el hospedador para mitigar el daño tisular consecuencia de la activación de la respuesta inmune. Esta revisión tiene como propósito actualizar los conceptos modernos en tolerancia inmune, con especial énfasis en el papel de las células Treg en la tolerancia inducida durante el curso de infecciones crónicas.

The immune system has the capability of protection against infectious disease which is accomplished by an enormous repertoire of receptors specifically reactive to foreign antigens, but it is tolerant to self-antigens, establishing biological identity. The ability to discriminate between self and non-self is a central property of the immune system, by using complex network of cellular and molecular mechanisms in order to prevent autoimmunity; this function is called immune tolerance. Thus, the Interaction between immune system and antigens is required for the generation of tolerance and it is critical in different physiological and pathological conditions in order to limit the damage to self tissues. Since Medawar description, who showed that the tolerance is an acquired property playing a central role in the homeostasis, several mechanism has been proposed to explain it. It is accepted today that an important group of antigen specific cells called regulatory T cell, both natural and induced, are critical as a unifying mechanism to maintain self-tolerance. These suppressor lymphocyte subpopulations had shown to play an important role not only by controlling autoimmune disease but also in the pathogenesis of many chronic infectious diseases, either manipulated by the microorganism to escape from the immune system, or induced by the host to reduce inflammatory damage. This review has the intention of updating about modern concepts in immune tolerance mechanisms, with special emphasis played by Treg cell in the tolerance which is unquestionable induced during the course of chronic infections diseases.

Estudio del efecto inmunomodulador de la Equinácea purpúrea en pacientes con herpes labial recurrente / Imunomodulatory effects of Echinacea purpurea in patients with recurrent herpes labialis

Introducción: El Herpes Labial Recurrente supone una condición inmunológica alterada, tal como una hiperactividad de células T-reguladoras CD4+CD25+ (Treg). Éstas ejercen control sobre la tolerancia periférica y reducen el riesgo inmunopatológico, suprimiendo otras líneas celulares. Por ende, la supresión ejercida sobre la reacción inmune antiviral podría afectar negativamente el curso de la infección. Este contexto ha impulsado la búsqueda de nuevas alternativas inmunomoduladoras como la Equinácea purpúrea. Dada su propiedad inmunosupresora, se propone en el tratamiento del Herpes Labial Recurrente. Metodología: Estudio clínico prospectivo que analiza las subpoblaciones linfocitarias en 12 pacientes con Herpes Labial Recurrente, antes y después de recibir Equinácea purpúrea (30 gotas tres veces al día durante siete días).Resultados: En comparación con individuos sanos, los pacientes presentan una respuesta aumentada de células Treg. Esta condición se reduce significativamente tras recibir Equinácea purpúrea (515 + 145 y 432 + 113 cel/mm3 antes y después del tratamiento, respectivamente, p < 0,005). Conclusión: La hiperactividad de células Treg podría explicar el estado de inmunosupresión de estos pacientes y favorecería la persistencia viral. Se propone esta fitomedicina como una alternativa inmunoterapéutica beneficiosa.

Background: Recurrent Herpes Labialis patients may suffer from immunological alterations, such as CD4+CD25+Regulatory-T Cell (Treg) hyperactivity. These cells control peripheral tolerance and reduce immunopathology risk by suppressing other immunological cells. Hence, the Treg cell suppression on the antiviral immune reaction may perturb adversely the herpes infection outcome. This scenario has forced physicians to explore new immunomodulatory alternatives in Phytomedicine, such as Echinacea purpurea. Regarding the immunosuppressive property, it has been challenged to be employed in the Recurrent Herpes Labialis management. Methods: Clinical prospective study that analyzed lymphocytic subpopulation profile in twelve patients with Recurrent Herpes Labialis, before and after receiving E. purpurea (30 drops three times a day during seven days). Results: Comparing to healthy subjects, patients presented an enlarged Treg cell response. This condition became significantly reduced after receiving E. purpurea. (515 + 145 and 432 + 113 cel, before and after treatment respectively, p < 0.005). Conclusion: The intensified Treg cell activity may elucidate the immune suppression these patients undergo, aiding the viral persistence and survival. This proposes E. purpurea asa beneficial immunotherapeutic alternative.

Células T reguladoras naturales durante la infección por el VIH: el tejido linfoide como blanco primario de la replicación viral / Natural regulatory T cells during HIV infection: lymphoid tissue as the primary target of viral replication

La infección por el VIH se asocia con una inmunodeficiencia secundaria grave que lleva a la aparición de infecciones oportunistas y procesos oncogénicos. En el curso de esta infección se observan comúnmente alteraciones de la inmunidad mediada por células T y células presentadoras de antígeno; en la actualidad se considera que ciertas poblaciones celulares con propiedades inmunorreguladoras son en parte responsables de estas alteraciones. De hecho, en los principales sitios de replicación viral, como los órganos linfoides y el tejido linfoide asociado a la mucosa gastrointestinal, se han observado alteraciones funcionales y cuantitativas en la subpoblación de células T reguladoras (Treg). Aunque se desconoce el papel de estas células en la patogénesis de la infección por el VIH, los estudios sugieren que podría ser dual: 1) proteger del daño tisular y de la eliminación de células T CD4+ causados por la hiperactivación inmunológica; 2) contribuir a la patogénesis de esta infección viral. La acumulación de células Treg funcionales afecta el desarrollo de respuestas inmunes específicas que permiten la eliminación del patógeno, facilitando de esta manera su permanencia en los tejidos. En esta revisión se presenta la evidencia científica disponible sobre el efecto de las células Treg en la patogénesis de la infección por el VIH.

HIV infection is associated with a severe secondary immunodeficiency leading to opportunistic infections and malignancies. Alterations of the cellular immunity mediated by T cells and antigen presenting cells are common characteristics of this infection. Recently, it has been proposed that the immunoregulatory properties of several cell populations are partially responsible for these alterations. In fact, functional and quantitative alterations of the regulatory T cell (Treg) subpopulation have been described in sites of active viral replication such as lymphoid organs and the lymphoid tissue associated with the gastrointestinal mucosa. Although the role of Treg in HIV pathogenesis is unknown, different studies suggest that it could be dual: (1) to protect from tissue damage and from CD4+ T cell elimination caused by the immune hyperactivation; (2) to contribute to HIV pathogenesis. The accumulation of functional Tregs affects the development of the specific immune responses that would allow elimination of the pathogen, thus favouring its permanence in different tissues. This review presents the scientific evidence available on the effect of Treg cells during the pathogenesis of HIV infection.

Células T reguladoras, infección y autoinmunidad: implicaciones en terapéutica / Regulatory T cells, Infection and Autoimmunity. Therapeutic implications

El entendimiento del equilibrio del sistema inmune es, además de una pregunta aún no resuelta, una esperanza para el principio de la terapéutica en enfermedades que le siguen ganando la batalla al ejercicio médico. La respuesta inmune innata permite la diferenciación de lo propio y lo extraño mediante receptores de reconocimiento de patrones moleculares asociados a patógenos que activan las células presentadoras de antígeno cuando se unen con moléculas estructural y químicamente conservadas entre los patógenos. Sin embargo, el sistema inmune se torna tan complejo que estos controles iniciales no son suficientes para un funcionamiento perfecto. La presencia de enfermedades autoinmunes continúa sin una explicación absoluta y la señal de cuándo apagar una respuesta inmune no está completamente entendida hasta ahora. El redescubrimiento de las células T reguladoras satisface no sólo explicaciones del equilibrio inmune sino que también se convierte en un blanco terapéutico muy seductor para el anhelado control de la respuesta inflamatoria, fenómenos infecciosos y autoinmunes. Consecuente con esto, la célula T reguladora explicaría cómo las infecciones que estimulan su proliferación puedan ser protectoras de autoinmunidad independiente de la carga genética o medio ambiente en que se desarrolle el individuo. Las infecciones que, por el contrario, eliminen o inactiven las células T reguladoras, favorecen la presencia de autoinmunidad. Se consultaron únicamente artículos en inglés o español en la bases de datos PubMed hasta la fecha de envío del artículo.

The mechanisms underlying the control of the immune system are still incompletely solved. The treatment of many human diseases is still a medical challenge. The innate immune system recognizes the difference between self and non-self antigens through the binding of pathogen associated molecular patterns to pattern recognition receptors present on the antigen presenting cells. The recent rediscovered regulatory T cells participate in the immune system homeostasis. On the other hand, regulatory T cells may be incriminated in the pathology of both inflammatory and infectious diseases. Thus, these cells would be a suitable target for the treatment of diseases in which they are involved. The participation of regulatory T cells in some infectious diseases could explain why there is an opposite association between some infectious diseases such as tuberculosis and autoimmune diseases. As a corollary, depletion or inactivation of regulatory T cells could facilitate the development of autoimmune phenomena.