Patients With Atopic Dermatitis Sensitized to Pet Dander Mount IgE and T-Cell Responses to Mammalian Cystatins, Including the Human Self-Protein

Background: Immediate and delayed-type hypersensitivity reactions to pet-borne allergens are common in atopic diseases. In atopic dermatitis (AD), controversy surrounds the contribution to the disease of cross-reactivity to self-proteins. Human cystatin A and the cat allergen Fel d 3 belong to the cystatins, an evolutionary conserved protein family. The objective of the present study was to assess crossreactivity between mammalian cystatins and to analyze T-cell responses to cystatin in AD patients sensitized to pet dander. Methods: cDNA coding for dog cystatin was cloned from dog skin. Sera from 245 patients with IgE-mediated sensitization to cat and dog dander were tested for IgE binding to recombinantly expressed feline, canine, and human cystatin. Of these, 141 were also diagnosed with AD. Results: Cystatin-specific IgE was detected in 36 patients (14.7%), of whom 19 were considerably affected by AD. Within the AD patients, 9 had measurable IgE against all 3 cystatins. Cystatin-sensitized AD patients did not differ from non–cystatin-sensitized patients in terms of disease severity, age, or total IgE levels. T-cell cytokine measurements showed elevated IL-4 levels after stimulation with feline and human cystatin. Conclusion: The humoral response suggests that in addition to Fel d 3, the homologous protein from dog might play a role in allergy. Furthermore, human cystatin appears to be capable of driving a type 2 immune response in sensitized AD patients and may therefore be considered a so-called autoallergen, as proposed for other evolutionary conserved proteins. (AU)

Antecedentes: Las reacciones de hipersensibilidad de tipo inmediato y retardado a los alérgenos que están en las mascotas son comunes en las enfermedades atópicas. En este estudio, en pacientes con dermatitis atopica (DA), se analiza la reactividad cruzada con las autoproteínas y su contribución a la enfermedad. Tanto la cistatina A humana como el alérgeno felino Fel d 3 pertenecen a la familia de las cistatinas, una familia de proteínas conservadas evolutivamente. El objetivo del presente estudio fue evaluar la reactividad cruzada entre las cistatinas de mamíferos y analizar la respuestas de las células T a la cistatina en pacientes con DA sensibilizados a la caspa de las mascotas. Métodos: El ADNc que codifica la cistatina de perro se clonó a partir de piel de perro. Se analizaron sueros de 245 pacientes con sensibilización por IgE a la caspa de gato y perro para determinar la unión de IgE a cistatina felina, canina y humana expresada de forma recombinante, respectivamente. De estos 245 pacientes, 141 fueron diagnosticados de DA. Resultados: Se detectó IgE específica frente a cistatina en el 14,7% (36) de los pacientes, de los cuales 19 padecían DA. Dentro de los pacientes con DA, 9 tenían IgE medible contra las tres cistatinas. Los pacientes con DA sensibilizados frente a cistatina no difirieron de los pacientes no sensibilizados con cistatina en términos de gravedad de la enfermedad, edad o niveles totales de IgE. El análisis de citocinas de células T reveló niveles elevados de IL-4 después de la estimulación con cistatina felina y humana. Conclusión: La respuesta humoral sugiere que, además de Fel d 3, la proteína homóloga de perro también podría desempeñar un papel en la alergia. Además, la cistatina humana parece ser capaz de promover una respuesta inmune de tipo 2 en pacientes con DA sensibilizados y, por lo tanto, puede considerarse un autoalérgeno, como se ha propuesto para otras proteínas conservadas evolutivamente. (AU)

EBER + extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia / Linfoma T/NK EBER positivo en paciente con linfocitopenia CD4 idiopática

Abstract Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the im munosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon asso ciation of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months

Resumen La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndro me, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

Uso da eletromiografia de superfície na resultância do treinamento muscular inspiratório com carga linear em portadores do vírus linfotrópico humano tipo 1 / Use of surface electromyography in results of inspiratory muscle training with linear load in patients with type 1 human lymphotropic virus

Este estudo visa avaliar por eletromiografia de superfície o comportamento dos músculos inspiratórios no treinamento muscular em voluntários com vírus linfotrópico de célula T humana do tipo 1. Trata-se de um ensaio clínico. Sete voluntários, com idade 58,85 ± 7,2) anos, realizaram treinamento muscular inspiratório domiciliar por 4 semanas, 3 vezes por semana, 30 minutos diários por meio de incentivador de carga linear. Para avaliação utilizou-se os dados de pressão inspiratória máxima e os dados da eletromiografia de superfície nas fases pré (T0), segunda semana (T2) e após a quarta semana (T4) de treinamento. Observou-se aumento progressivo da força muscular inspiratória de T0 a T4 (p = 0,007), assim como, aumento do recrutamento das unidades motoras pela análise da amplitude do sinal eletromiográfico, sendo mais evidente para o músculo esternocleidomastóideo (p = 0,12) em comparação ao músculo diafragma (p = 0,6). Verificou-se que no decurso do treinamento muscular ocorreu melhora significativa da força muscular inspiratória com maior recrutamento das fibras musculares dos músculos analisados na amostra. (AU)

This study aimed to evaluate by surface electromyography the behavior of inspiratory muscles in the muscle training of volunteers with human T-cell lymphotropic virus type 1. This was a clinical trial. Seven volunteers, 58,85 ± 7.21 years old, underwent inspiratory muscle training at home for 4 weeks, 3 times a week, 30 minutes daily by means of a linear load stimulator. The maximum inspiratory pressure data and the surface electromyography data were used for evaluation in the pre (T0), second week (T2) and after the fourth week (T4) training phases. There was a progressive increase in inspiratory muscle strength from T0 to T4 (p = 0.007), as well as an increase in the recruitment of motor units by analyzing the amplitude of the electromyographic signal, being more evident for the sternocleidomastoid muscle (p = 0.12) in comparison to the diaphragm muscle (p = 0.6). During the muscle training inspiratory muscle strength improves with greater recruitment of muscle fibers from the muscles analyzed in the sample. (AU)

Interleukin-5 levels are decreased in the plasma of coronary artery disease patients and inhibit Th1 and Th17 differentiation in vitro.

INTRODUCTION AND OBJECTIVES: Interleukin (IL)-5 is an anti-inflammatory cytokine that has been demonstrated to be involved in cardiovascular diseases, including aortic aneurysm and heart failure. This study aimed to investigate the involvement of IL-5 in coronary artery disease (CAD) and the possible mechanisms. METHODS: We analyzed IL-5 expression in human coronary artery specimens collected from CAD patients and deceased donors. Plasma IL-5, IL-17, and interferon-γ levels in CAD patients were detected using ELISA kits, with samples from chest pain patients (non-CAD) as controls. Mouse CD4+T helper (Th) cells were separated, and the effect of IL-5 on Th1, regulatory T cell and Th17 differentiation and mRNA levels of their characteristic cytokines were detected using flow cytometry and reverse transcription-quantitative polymerase chain reaction, respectively. RESULTS: IL-5 was significantly decreased in the coronary plaque of CAD patients compared with the deceased donors group, and IL-5 was mainly derived from macrophages in the coronary artery plaque. Compared with the non-CAD group, plasma IL-5 levels in the CAD groups were significantly lower, and the sequence from high to low was stable angina pectoris, unstable angina pectoris, and acute myocardial infarction. Binary linear regression analysis showed that IL-5 was independently correlated with the occurrence of CAD. Recombinant mouse IL-5 treatment decreased Th1 and Th17 levels and mRNA expression of their characteristic cytokines in oxidized low-density lipoprotein-treated CD4+Th cells. CONCLUSION: IL-5 levels were decreased in CAD patients and inhibited oxidized low-density lipoprotein Th1 and Th17 differentiation in vitro.

O feto é um ser alogênico de sucesso / The fetus is a successful allogeneic being

O feto é um ser alogênico de sucesso. O feto é um aloenxerto natural bem tolerado pelo organismo materno. Vários fatores contribuem para a tolerância materna ao feto: 1. O útero é um local do corpo imunologicamente privilegiado, protegido por uma barreira tecidual não imunogênica; 2. A promoção de uma resposta imunossupressora local pela mãe: a. A molécula HLA-G do MHC de classe Ib, expressa nas células da placenta, impede que as células NK matem a placenta; b. A catabolização do aminoácido essencial triptofano pela placenta impede que as células T da mãe tenham acesso ao feto; c. A secreção das citocinas TGF-ß, IL-4 e IL-10, pelo epitélio uterino e trofoblasto, tende a suprimir as respostas das células T da mãe; d. A secreção das citocinas TGF-ß e IL-10, pelas células T reguladoras, também inibe as respostas de células T maternas.(AU)

The fetus is a successful allogeneic being. The fetus is a natural allograft well tolerated by the maternal organism. Several factors contribute to maternal fetal tolerance: 1. The uterus is an immunologically privileged body site, protected by a non-immunogenic tissue barrier. 2. Promoting a local immunosuppressive response by the mother: a. The MHC class Ib HLA-G molecule, expressed on placental cells, prevents NK cells from killing the placenta; b. The catabolization of the essential amino acid tryptophan by the placenta prevents the mother's T cells from accessing the fetus; c. Secretion of TGF-ß, IL-4 and IL-10 cytokines by the uterine and trophoblast epithelium tends to suppress the T-cell responses of the mother; d. Secretion of TGF-ß and IL-10 cytokines by regulatory T cells also inhibits maternal T cell responses.(AU)

Activación de la célula T, alteraciones en el lupus eritematoso sistémico, una revisión narrativa / T-cell activation, alterations in systemic lupus erythematosus: A narrative review

Resumen La activación de los linfocitos T se inicia a través de la presentación de antígenos endógenos o exógenos por células presentadoras de antígenos a través del complejo mayor de histocompatibilidad, el cual se une a un receptor especializado presente en los linfocitos T. Este reconocimiento desencadena una cascada de señalización intracelular que conlleva a un aumento en la expresión de integrinas, modificaciones del citoesqueleto y producción de factores de transcripción involucrados en la liberación de citocinas y mediadores inflamatorios. Uno de los inductores más importantes en la activación celular es el complejo enzimático con acción tirosina cinasa. Las cinasas que pertenecen a la familia SRC (SFK), FYN y LCK están involucradas en un gran número de procesos importantes en la activación, modulación de la respuesta linfocitaria y el desarrollo de enfermedades autoinmunes. La regulación de la señalización de las cinasas, así como de proteínas adaptadoras involucradas en la activación del linfocito T, son fundamentales para mantener el umbral de activación y modulación de la respuesta del linfocito. La fosforilación de sitios de regulación positiva de estas proteínas es importante para permitir una configuración activa de la proteína y de esta forma su máxima capacidad como cinasa. La fosforilación de los sitios de regulación negativa conlleva a una configuración cerrada de la proteína de tal forma que reduce su función de cinasa e inhibe su función. Las alteraciones en la señalización por modificación de algunas proteínas citoplasmáticas se asocian en algunos casos al desarrollo de enfermedades autoinmunes, como el lupus eritematoso sistémico. En condiciones fisiológicas, el complejo receptor de linfocitos T se reagrupa con complejos proteicos que interactúan armónicamente para generar una sen al interna. Los eventos de señalización alterados son en parte los responsables de una expresión anómala de citocinas, entre ellas la interleucina-6 (IL-6), IL-10, IL-2, IFN y CD40 ligando; estas modificaciones alteran la capacidad de los linfocitos T para sobre estimular a los linfocitos B, traduciéndose en un aumento en la producción de autoanticuerpos y en el desencadenamiento de la enfermedad autoinmune.

Abstract The activation of T cells is initiated by the presentation of exogenous or endogenous antigens, by antigen presenting cells through the major histocompatibility complex, which binds to a special receptor on T cells. This acknowledgement triggers a cascade of intracellular signalling that leads to an increase in integrin expression, cytoskeletal modifications, and transcription factors production involved in the liberation of cytokines and inflammatory mediators. One of the most important inducers in cell activation is the enzymatic complex with tyrosine kinase action. The kinases which belong to the SRC (SFK) LCK and FYN family have been involved in a large number of important processes in the activation and modulation of the T cells response, as well as in the development of autoimmune diseases. Regulating the kinases signalling, as well as the adapter proteins involved in T cell activation, is essential for maintaining an activation threshold, as well as the modulation of cell response. The phosphorylation of the positive regulation sites of these proteins is important to allow an active configuration of the protein and thereby its maximum capacity as kinase. The phosphorylation of negative regulation sites leads to a closed configuration of the protein that reduces its kinase function, and thereby inhibits its own function. The alteration in signalling by the modification of certain cytoplasmic proteins in some cases is associated with the development of autoimmune diseases, such as systemic lupus erythematosus. Under physiological conditions the T cell receptor complex regroups with protein complexes that interact harmonically to generate an internal signal. The altered signalling events are partly responsible for an anomalous expression of cytokines, including the interleukin-6 (IL-6), IL-10, IL-2, IFN, and CD40 linking, these modifications affects the cells ability to over-stimulate T and B cells, resulting in an increased production of autoantibodies and the triggering of the autoimmune disease.

Defectos en la expresión de cadena zeta en un grupo de pacientes con lupus, escleroderma y artritis de inicio tardío, Colombia 2014 / Defects in the Zeta Chain Expression in a Group of Patients with SLE, Scleroderma and Late-onset Arthritis, Colombia 2014 / Defeitos na expressão de cadeia zeta em um grupo de pacientes com Lúpus, Esclerodermia e artrite de início tardio, Colômbia 2014

Introducción: El lupus eritematoso sistémico (LES), la escleroderma y la artritis de inicio tardío son enfermedades inflamatorias autoinmunes (EIA) caracterizadas por la producción de autoanticuerpos y presencia de células T anormales, las cuales generan respuesta inmune defectuosa. La expresión anormal de moléculas clave en señalización y la función defectuosa de los linfocitos T cumplen un papel significativo en la patogénesis de la enfermedad autoinmune. Las células T muestran numerosas anormalidades en la señalización del complejo receptor de célula T cadena zeta (TCRζ) estas aberraciones resultan en la alteración de la expresión de citoquinas y algunos eventos bioquímicos involucrados en la expresión de moléculas de superficie. Los defectos en el complejo TCRζpueden estar asociados al uso de corticoides, utilizados en pacientes con enfermedad autoinmune, debido a su potente actividad antiinflamatoria y propiedades inmunosupresoras. Los corticoides sintéticos como la dexametasona inhiben la actividad trascripcional de algunos factores como NFkB y AP-1 los cuales regulan la síntesis de algunas citoquinas y podrían estar involucrados en la síntesis de TCRζ. Objetivos: Evaluar la asociación de los defectos de la expresión de cadena zeta (ζ), en células T de pacientes con enfermedad autoinmune sin tratamiento con corticoides. Los defectos en la expresión defectuosa de zeta, proteína asociada al receptor TCR, altera la activación normal del linfocito T. Materiales y métodos: Estudio analítico de casos y controles, con una relación 1:1 (13:13). Los casos fueron pacientes con enfermedad autoinmune activa (6 pacientes con LES, 5 pacientes con escleroderma y 2 pacientes con artritis de inicio tardío), y que no hubieran iniciado tratamiento con corticoides, los controles fueron pacientes sin diagnóstico de enfermedad autoinmune. El diagnóstico se hizo a través de los criterios establecidos por el Colegio Americano de Reumatología para pacientes con LES, escleroderma y artritis de inicio tardío. Se realizó venopunción extrayendo 10ml de sangre total, se extrajo RNA total y se hizo RT PCR, se amplificó utilizando un juego de primers que flanquean una región de 138 pares de bases que involucraban los exones 2, 3 y 4 de cadena ζ. Resultados: En los valores de amplificación de cadena Z se encontraron diferencias significativas en pacientes con enfermedad autoinmune (0,8214±0,1787, med=0,7368) comparada con el grupo control (0,9225±0,1272, med=0,9830) (p=0,045, Test no-paramétrico, exacto de Mann Whitney a una cola). Conclusión: La expresión de cadena Z se encontró disminuida en células T de pacientes con enfermedad autoinmune, sin uso de corticoides, la disminución o una falta de expresión de la cadena Z puede causar alteraciones en la respuesta inmune.

Introduction: Systemic Lupus Erythematosus (SLE), Scleroderma and late-onset arthritis are autoimmune inflammatory diseases (EIA) characterized by autoantibody production and presence of abnormal T cells which generate defective immune response. The abnormal expression of key signaling molecules in the defective function of T-lymphocytes plays a significant role in the pathogenesis of autoimmune disease. The T-cells exhibit numerous abnormalities TCRζ1 signaling complex, these aberrations result in altered expression of cytokines and some biochemical events involved in the expression of surface molecules. Defects in the complex may be associated TCR ζ to steroids used in autoimmune disease patients due to their powerful anti- inflammatory activity and immunosuppressive properties. The synthetic corticosteroids such as dexamethasone inhibit the transcriptional activity of some factors such as NFKB and AP-1, which regulate the synthesis of certain cytokines and could be involved in the TCRζ synthesis. Material and Methods: A case-control study, with a 1:1 ratio of cases and controls (13:13). Cases were patients with active autoimmune disease (6 patients with SLE, 5 patients with scleroderma and 2 patients with lateonset arthritis), who have not started treatment with corticosteroids. Controls were patients with no autoimmune disease. The diagnosis was made by the criteria established by the American College of Rheumatology for patients with SLE, scleroderma and late-onset arthritis. A 10 mL sample was obtained by venipuncture whole blood. Total RNA was extracted and RT-PCR was performed using a set of primers flanking a region of 138 base pairs involving exons 2, 3 and 4 of the ζchain. Results: The values of Z chain amplification showed significant differences in patients with autoimmune disease (0.8214 ± 0.1787, med = 0.7368) compared with the control group (0.9225 ± 0.1272, med = 0.9830) (p = 0.045, Mann-Withney non-parametric one tailed exact test). Conclusion: We observed a reduced level of in the zeta chain expression in T cells in patients with autoimmune disease without use of corticosteroids.

Introdução: O Lúpus Eritematoso Sistêmico (LES), Esclerodermia e Artite de início tardio são doenças inflamatórias autoimunes caracterizadas por produção de autoanticorpos e presença de células T anormais as quais geram resposta imune defeituosa. A expressão anormal de moléculas chave em sinalização e a função defeituosa dos linfócitos T cumprem um papel significativo na patogênese da doença autoimune. As células T mostram numerosas anormalidades na sinalização do Complexo Receptor de célula T cadeia zeta (TCRζ)1, estas aberrações resultam na alteração da expressão de citocinas e alguns eventos bioquímicos envolvidos na expressão de moléculas de superfície. Os defeitos no complexo TCRζ podem estar associados ao uso de corticoides, utilizados em pacientes com doença autoimune devido a seu potente atividade auto-inflamatória e propriedades imunossupressoras. Os corticoides sintéticos como a dexametasona inibem a atividade transcricional de alguns fatores como NFkB e AP-1 os quais regulam a síntese de algumas citocinas e poderiam estar envolvidas na síntese de TCRζ2, 3. Objetivos: Avaliar a associação dos defeitos da expressão de cadeia zeta (ζ), em células T de pacientes com doença autoimune sem tratamento com corticoides. Os defeitos na expressão defeituosa de zeta, proteína associada ao receptor TCR altera a ativação normal do linfócito T. Materiais e métodos: Estudo analítico de casos e controles, com uma relação 1:1 (13:13). Os casos foram pacientes com doença autoimune ativa (6 pacientes com LES, 5 pacientes com esclerodermia e 2 pacientes com artrite de início tardio), e que não tenham iniciado tratamento com corticoides e os controles foram pacientes sem diagnóstico de doença autoimune. O diagnóstico se fez através dos critérios estabelecidos pelo Colegio Americano de Reumatología para pacientes com LES, esclerodermia e artrite de início tardio. Se realizou venopunção extraindo 10mls de sangue total, se extraiu RNA total e se fez RT PCR, se amplificou utilizando um jogo de primers que flanqueiam uma região de 138 pares de bases que envolviam os exões 2, 3 e 4 de cadeia ζ. Resultados: Nos valores de amplificação de cadeia Z se encontraram diferenças significativas em pacientes com doença autoimune (0.8214±0.1787, med=0.7368) comparada com o grupo controle (0.9225±0.1272, med=0.9830) (p=0.045, Teste não paramétrico, exato de Mann Whitney) Conclusão: A expressão de cadeia Z encontrou-se diminuída em células T de pacientes com doença autoimune, sem uso de corticoides, a diminuição ou uma falta de expressão da cadeia Z pode causar alterações na resposta imune.

Immune function of peripheral T cells in patients with venous thromboembolism or coronary artery atherosclerosis.

INTRODUCTION AND OBJECTIVES: Recent studies have shown that the major risk factors for arterial thrombotic diseases are closely associated with venous thromboembolism (VTE). This study aimed to investigate the expression of CD3, CD4 and CD8 in T lymphocytes, the CD4/CD8 ratio and high-sensitivity C-reactive protein (hs-CRP) levels in patients with VTE, coronary artery atherosclerosis (CAA) and healthy subjects. METHODS: A total of 82 healthy subjects, 51 VTE patients and 114 CAA patients were recruited, and the expression of CD3, CD4 and CD8 in T lymphocytes and the CD4/CD8 ratio were determined. Serum hs-CRP was also measured. RESULTS: Compared to healthy subjects, VTE patients had significantly reduced CD3 expression (p=0.019), comparable CD4 expression (p=0.868), significantly reduced CD8 expression (p<0.001) and increased CD4/CD8 ratio (p=0.044). However, VTE patients had comparable expression of CD3, CD4 and CD8 and CD4/CD8 ratio to CAA patients. In addition, among patients with VTE or CAA, the proportion of patients with reduced CD3+ and CD8+ T lymphocytes or increased CD4/CD8 ratio was significantly higher than in healthy subjects. In addition, hs-CRP in both VTE and CAA groups was significantly higher than in healthy subjects. CONCLUSIONS: The antigen recognition and signal transduction activation of T cells is significantly reduced in patients with VTE or CAA, and the killing effect of T cells on pathogens, including viruses, is also significantly compromised. In addition, inflammatory and immune mechanisms are involved in the occurrence and development of venous and arterial thrombosis.

La molécula CD28 y su función en la activación de células T

La molécula CD28 es considerada uno de los receptores coestimuladores más importantes en las células T, necesaria para la completa activación celular. En los últimos años se ha acumulado suficiente evidencia sobre su participación en los mecanismos conocidos como señal 2 de activación celular o coestimuladora. De esta forma se convierte en un blanco atractivo para estrategias terapéuticas en enfermedades autoinmunes y trasplante de órganos. Esta revisión se concentra en los principales mecanismos por los cuales esta molécula participa en la completa activación de las células T(AU)

CD28 is a very important correceptor among T cells and provide positive signals that promote and sustain T-cell responses. In the last few years, CD 28 has become an interesting target in grafts and autoimmune diseases. This review will focus on the mechanisms whereby CD28 allowing a complete T cell activation(AU)

La molécula CD28 y su función en la activación de células T

La molécula CD28 es considerada uno de los receptores coestimuladores más importantes en las células T, necesaria para la completa activación celular. En los últimos años se ha acumulado suficiente evidencia sobre su participación en los mecanismos conocidos como señal 2 de activación celular o coestimuladora. De esta forma se convierte en un blanco atractivo para estrategias terapéuticas en enfermedades autoinmunes y trasplante de órganos. Esta revisión se concentra en los principales mecanismos por los cuales esta molécula participa en la completa activación de las células T

CD28 is a very important correceptor among T cells and provide positive signals that promote and sustain T-cell responses. In the last few years, CD 28 has become an interesting target in grafts and autoimmune diseases. This review will focus on the mechanisms whereby CD28 allowing a complete T cell activation

Células T y sus receptores αß y γδ en biopsias de pacientes con enfermedad periodontal / T cells and its receptords and αß and γδ in biopsies from patients with periodontal disease

El propósito de este estudio es determinar la presencia y localización de las células T y de sus receptores αβ y γδ en biopsias de tejido gingival de pacientes con enfermedad periodontal. Se evaluaron 60 biopsias de 12 pacientes, 4 con diagnostico de periodontitis agresiva, 4 con periodontitis crónica y 4 con gingivitis, las cuales fueron procesados para su análisis histológico, inmunohistoquímico e histomorfometrico. Al analizar los resultados por diagnostico los marcadores que mas predominaron fueron, en Gingivitis CD3, CD8 y TCR γδ en tejido conectivo. En Periodontitis crónica CD3, CD8 y TCR γδ en epitelio oral y CD4 el cual presentó una expresión homogénea en los tejidos analizados. En periodontitis agresiva CD3 y CD8 en epitelio crevicular, con una distribución similar entre CD4 y CD8 tanto en epitelio oral como en tejido conectivo y TCR γδ en conectivo. En cuanto a las cadenas variables del TCR Vβ los más expresados en las diferentes patologías estudiadas fueron el 6.7, 8.1 y 12 a nivel del tejido conectivo. Los estudios sobre la expresión de estas familias parecen indicar que es otra vía de activación a tener en cuenta dentro del modelo de la patogenia de la enfermedad y que debe ser estudiado en modelos longitudinales en pacientes con pérdida de inserción progresiva.

T the purpose of this study is identifying the presence and localization of T cells and their receptor αβ and γδ in biopsies of gingival tissue in patients with periodontal disease. 60 biopsies were evaluated in 12 patients, 4 patients with diagnosis of gingivitis, 4 patients with chronic periodontitis and 4 with aggressive periodontitis, which were processed for the histological, immunohistochemical and histomorphometric analysis. The results by diagnosis showed that in gingivitis the more predominant markers were CD3, CD8 and TCR γδ in connective tissue. In chronic periodontitis the markers with bigger expression were CD3, CD8 and TCR γδ in oral epithelium and CD4 that showed a homogeneous behavior in the analized tissues. In aggressive periodontitis CD3 and CD8 in surcular epithelium, TCR γδ in connective tissue and CD4 and CD8 with a similar distribution in oral epithelium and connective tissue. In relation with variable chains of TCR Vβ, the most predominat in the different diagnosis were 6.7,8.1 and 12 in connective tissue. The investigations about the expression of these families indicate that it can be other important via of activation in the pathogenesis of periodontal disease and it should be study in longitudinal models in patients with progressive loss of attachment level.

Bases moleculares de la inmunología del cáncer / Molecular basis of cancer immunology

El sistema inmune es una red intrincada en la que participan diferentes tipos de células y de moléculas. La acción coordinada de todos sus elementos permite que se desarrolle una respuesta eficaz contra la célula tumoral. Sin embargo, los tumores presentan diversos mecanismos de evasión que permiten el desarrollo del mismo. En esta revisión se presentan eventos celulares y moleculares que participan en la regulación de la respuesta inmune contra tumores. Se discute la interacción de distintas moléculas como las del complejo principal de histocompatibilidad, receptor de antígenos de linfocitos T, moléculas de adhesión, antígenos tumorales y citocinas, así como lo más reciente sobre los mecanismos de escape tumoral e inmunoterapia

The immune system is a tight network of different types of cells and molecules. The coordinated action of these elements mounts a precise immune response against tumor cells. However, these cells present several escape mechanisms, leading to tumor progression. This paper shows several cellular and molecular events involved in the regulation of the immune response against tumor cells. The interaction of several molecules such as MHC, TcR, adhesins, tumor antigens and cytokines are discussed, as well as the most recent knowledge about escape mechanisms and immunotherapy.