Cytokine-induced killer cells: new insights for therapy of hematologic malignancies.

BACKGROUND: Cytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC-unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment-related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies. MAIN BODY: CIK cells consist of CD3+/CD56+ natural killer (NK) T cells, CD3-/CD56+ NK cells, and CD3+/CD56- cytotoxic T cells. In this regard, the CD3+/CD56+ NK T cells are the primary effectors. Compared with the previously reported antitumor immune cells, CIK cells are characterized by improved in vitro proliferation and amplification, enhanced migration and invasive capacity to tumor region, more significant antitumor activity, and a broader antitumor spectrum. CIK cells can also induce death in tumor cells via numerous pathways and mechanisms. Hence, CIKs-based therapy has been used in various clinical trials and has shown efficacy with a very low graft versus host disease (GVHD) against several cancers, such as hematologic malignancies, even in relapsing cases, or cases not responding to other therapies. Despite the high content of T cells, CIK cells induce low alloreactivity and, thus, pose a restricted threat of GVHD induction even in MHC-mismatched transplantation cases. Phase 1 and 2 clinical trials of CIK cell therapy have also highlighted satisfactory therapeutic advantages against hematologic cancers, indicating the safety of CIK cells even in haploidentical transplantation settings. CONCLUSION: CIK cells have shown promising results in the treatment of hematologic malignancies, especially in combination with other antitumor strategies. However, the existing controversies in achieving desired clinical responses underscore the importance of future studies.

Cytokine-induced killer cells-mediated chlorin e6-loaded gold nanostars for targeted NIR imaging and immuno-photodynamic combination therapy for lung cancer.

Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique characteristics of killing and targeting malignant tumors. Herein, we report a facile strategy for synthesis of monodisperse gold nanostars (GNSs) based on PEGylation and co-loaded with the photosensitizer chlorin e6 (Ce6) to form GNSs-PEG@Ce6 NPs. Then employing CIK cells loading the as-prepared GNSs-PEG@Ce6 NPs to fabricate a CIK cells-based drug delivery system (GNSs-PEG@Ce6-CIK) for lung cancer. Among them, GNSs was functioned as transport media, Ce6 acted as the near-infrared (NIR) fluorescence imaging agent and photodynamic therapy (PDT), and CIK cells served as targeting vectors for immunotherapy, which can increase the efficiency of tumor enrichment and treatment effect. The results of cellular experiments demonstrated that GNSs-PEG@Ce6 NPs had good dispersibility, water solubility and low toxicity under physiological conditions, and the cultured CIK cells had strong anti-tumor properties. Subsequently, GNSs-PEG@Ce6-CIK could effectively inhibit the growth of A549 cells under the exposure of 633 nm laser, which showed stronger killing effect than that of GNSs-PEG@Ce6 NPs or CIK cells. In addition, they showed good tumor targeting and tumor synergistic killing activityin vivo. Therefore, GNSs-PEG@Ce6-CIK was constructed for targeted NIR fluorescence imaging, enhanced PDT and immunotherapy of lung cancer.

Discovering single cannabidiol or synergistic antitumor effects of cannabidiol and cytokine-induced killer cells on non-small cell lung cancer cells.

Introduction: A multitude of findings from cell cultures and animal studies are available to support the anti-cancer properties of cannabidiol (CBD). Since CBD acts on multiple molecular targets, its clinical adaptation, especially in combination with cancer immunotherapy regimen remains a serious concern. Methods: Considering this, we extensively studied the effect of CBD on the cytokine-induced killer (CIK) cell immunotherapy approach using multiple non-small cell lung cancer (NSCLC) cells harboring diverse genotypes. Results: Our analysis showed that, a) The Transient Receptor Potential Cation Channel Subfamily V Member 2 (TRPV2) channel was intracellularly expressed both in NSCLC cells and CIK cells. b) A synergistic effect of CIK combined with CBD, resulted in a significant increase in tumor lysis and Interferon gamma (IFN-g) production. c) CBD had a preference to elevate the CD25+CD69+ population and the CD62L_CD45RA+terminal effector memory (EMRA) population in NKT-CIK cells, suggesting early-stage activation and effector memory differentiation in CD3+CD56+ CIK cells. Of interest, we observed that CBD enhanced the calcium influx, which was mediated by the TRPV2 channel and elevated phosphor-Extracellular signal-Regulated Kinase (p-ERK) expression directly in CIK cells, whereas ERK selective inhibitor FR180204 inhibited the increasing cytotoxic CIK ability induced by CBD. Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. Conclusions: Taken together, CBD holds a great potential for treating NSCLC with CIK cell immunotherapy. In addition, we utilized NSCLC with different driver mutations to investigate the efficacy of CBD. Our findings might provide evidence for CBD-personized treatment with NSCLC patients.

The Therapeutic Potential of Cytokine-Induced Killer in Patients with Cancer.

Despite the promising results of immunotherapy, further experiments need to be considered because of several factors ranging from physical barriers to off-tumor adverse effects. It is surprising that adoptive cellular immunotherapy, particularly dendritic cell and cytokine-induced killer (DC-CIK) therapy, is far less emphasized in the treatment of cancer diseases. DC-CIK therapy in cancer patients presents auspicious results with low or no side effects, which should not be overlooked. More interestingly, almost all DC-CIK clinical trials are ongoing in China that highlight the limitations of therapeutic strategies and require large-scale research. To date, it is advisable to consider combination therapy with chemotherapy since it has shown promising outcomes with higher efficacy. In this article, the efficacy of DC-CIK therapy in patients with cancer is summarized by underscoring the lack of experiments on soft cancers on an unprecedented scale. In brief, DC-CIK therapy is a safe and effective therapeutic agent for malignant and nonmalignant diseases that enhances short-term and long-term effects.

Dendritic cell-cytokine killer combined with microwave ablation reduced recurrence for hepatocellular carcinoma compared to ablation alone.

BACKGROUND: Several international practice guidelines have recommended local ablation as the first-line treatment for early-stage hepatocellular carcinoma (HCC). OBJECTIVE: This study aims to investigate the synergetic anti-tumor impact of dendritic cell-cytokine killer (DC-CIK) combined with microwave ablation (MWA) for HCC. METHODS: This retrospective study included 1,141 patients from the American Joint Committee on Cancer stage I-II HCC, who were treated with therapeutic MWA. The immunotherapy group encompassing 40 patients received additional immunotherapy with DC-CIK, whereas the control group consisting of 1,101 patients was treated with MWA alone. Propensity score matching (PSM) with ratio of 1:3 was employed to balance selection bias. The oncological outcome and immune status were measured after combination therapy. RESULTS: The immunotherapy group patients exhibited significant longer disease-free survival (DFS, primary HCC: p= 0.036; recurrent HCC: p= 0.026). For patients with primary HCC, the recurrence frequency was reduced (p= 0.002), and recurrence interval (19 months vs. 9 months, p< 0.001) was prolonged in the immunotherapy group. Subgroup analysis revealed that patients ⩽ 60 years old, moderately-differentiated HCC, or co-infected with Hepatitis B Virus (HBV) had a significant benefit over DFS in the immunotherapy group. After combination therapy, the serum CD3+ (p= 0.049), CD8/CD28+ (p= 0.045) were elevated. CONCLUSION: Combination therapy with DC-CIK and MWA can significantly reduce the recurrence and prolong DFS, especially for patients ⩽ 60 years old or with moderately-differentiated HCC or co-infected with HBV.

Generation and assessment of cytokine-induced killer cells for the treatment of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Cytokine-induced killer (CIK) cells are an adoptive immunotherapy reported to have strong anti-tumour activity across a range of cancers. They are a heterogeneous mix of lymphoid cells generated by culturing human peripheral blood mononuclear cells with cytokines and monoclonal antibodies in vitro. In this study, we investigated the yield and function of CIK cells generated from patients with CRC liver metastases. We first showed that CIK cells generated in serum free medium X-VIVO 15 were comparable to those from RPMI medium with 10% FBS in terms of the number and percentages of the main subsets of cells in the CIK culture, and the intracellular levels of granzyme B and perforin, and the pro-inflammatory cytokines IL-2, IFN-γ and TNF-α. The CIK cells were cytotoxic to CRC cell lines grown in 2D cultures or as spheroids, and against autologous patient-derived tumour organoids. Donor attributes such as age, sex, or prior chemotherapy exposure had no significant impact on CIK cell numbers or function. These results suggest that functional CIK cells can be generated from patients with CRC liver metastatic disease, and support further investigations into the therapeutic application of autologous CIK cells in the management of patients with CRC liver metastases.

Cytokine-induced killer (CIK) cells, successes and challenges: report on the first international conference dedicated to the clinical translation of this unique adoptive cell immunotherapy.

On August 30, 2023, experts from Germany and abroad met to discuss the successes and challenges of cytokine-induced killer cell (CIK) therapy, that recently celebrated its 30th anniversary providing treatment for cancer. This first virtual conference was hosted by CIO Bonn, a certified Comprehensive Cancer Center (CCC) funded by German Cancer Aid (DKH). In addition to keynote speakers involved in CIK cell clinical trials or optimized preclinical models to improve this adoptive cell immunotherapy, more than 100 attendees from around the world also participated in this event. Initiatives to establish the International Society of CIK Cells (ISCC) and a stronger CIK cell network guiding preclinical research and future clinical trials were also announced.

Advances in research based on antibody-cell conjugation.

Antibody-cell conjugation (ACC) technology is a new research direction in medicine and biotechnology in recent years. The concept of ACC was proposed by Hsiao et al. and developed into a viable cell therapy technology, which refers to the cells with specific functions. Such as natural killer cells (NK cells), cytokine induced killer cells (CIK) and other immune cells and monoclonal antibodies through the linker together formed conjugate. ACC directly modifies specific antibodies on the cell surface through a simple and effective chemical coupling method to enable cells to have new functions. ACC has been developed for the treatment of various diseases, including cancers of the blood system and solid tumors. This paper reviews the current ACC construction methods, challenges and future development directions.

Análise do perfil fenotípico e funcional das células natural Killer e linfócitos TCD8+ no Líquen plano / Analysis of phenotypic and functional profile of Natural Killer cells and CD8 + T lymphocytes in Lichen planus

Líquen plano (LP) é uma doença mucocutânea de natureza inflamatória crônica de etiologia ainda desconhecida. Alterações na resposta imune inata, como aos padrões moleculares associados à patógenos (PAMPs) e padrões moleculares associados ao dano (DAMPs) podem levar à inflamação crônica e contribuir com a patogênese do LP. OBJETIVO: Avaliar o efeito da ativação via o DAMP S100A8 e o receptor Toll-like 4 (TLR-4) em células Natural killer (NK) e TCD8 citotóxicas e suas subpopulações de memória/efetoras em pacientes com LP. MÉTODOS: Foram selecionados 25 pacientes com LP (22 mulheres, 3 homens) com idade média de 43,46 anos ± 8,46 e um grupo controle com 25 indivíduos (22 mulheres, 3 homens) com idade média de 42 anos ± 5,5. A determinação transcricional e da expressão por imunohistoquimica dos DAMPs S100A8, HMGB-1 e de TLR-4 e RAGE foi realizada em biópsias de lesões cutâneas de indivíduos com LP, e os níveis séricos de S100A8, HMGB-1, MICA e MICB foram determinados por ELISA. As células mononucleares (CMNs) de sangue periférico foram avaliadas por citometria de fluxo quanto a frequência de TNF, IL-1beta e o marcador de desgranulação CD107a em células TCD8+ e células NK CD56+ e suas subpopulações. A avaliação da via de sinalização de TLR em células TCD8+ purificadas e ativadas com S100A8 foi analisada por PCR array e a determinação da expressão de mRNA dos componentes do inflamassoma em células TCD8+ ativadas com S100A8 por PCR em tempo real. RESULTADOS: Foi evidenciado nos indivíduos com LP elevada expressão da proteína S100A8 nas lesões cutâneas e de HMGB-1, TLR-4 e RAGE na derme, em paralelo ao aumento da expressão de mRNAs para S100A8 e S100A9 e diminuição de RAGE. Além disto, uma elevação dos níveis séricos do dímero S100A8/A9 foi detectada nos pacientes comparados aos controles, ao contrário do DAMP HMGB-1 que mostrou níveis similares em ambos os grupos. A influência do S100A8 em células TCD8+ e células NK, foi analisada em CMNs pela ativação...

Lichen planus (LP) is a mucocutaneous inflammatory chronic disease of unknown etiology. Alterations in the innate immune response such as the pathogen-associated molecular pattern (PAMPs) and damage-associated molecular pattern (DAMPs) can lead to chronic inflammation and contribute to the pathogenesis of LP. OBJECTIVE: Evaluate the effect of the activation trough the DAMP S100A8 and the Toll-like receptor 4 (TLR-4) on the Natural killer cells (NK) and cytotoxic TCD8 cells and their memory / effector subsets in LP disease. METHODS: We selected 25 patients with LP (22 women, 3 men) with a mean age of 43.46 years ± 8.46 and a control group of 25 subjects (22 women, 3 men) with a mean age of 42 ± 5, 5. The transcriptional determination and protein expression by immunohistochemistry of DAMPs, S100A8 and HMGB-1 as well as TLR-4 and RAGE was performed on biopsies of skin lesions from patients with LP, and serum levels of S100A8, HMGB-1, MICA and MICB were determined by ELISA. Peripheral blood mononuclear cells (PBMCs) were assessed by flow cytometry to evaluate the frequency of TNF, IL-1beta and the degranulation marker CD107a in CD8+ T cells and CD56 + NK cells and their subsets. The evaluation of the TLR signaling pathway in purified CD8 + T cells activated with S100A8 were analyzed by PCR array and the determination of mRNA expression of inflammasome components on CD8 + T cells activated by S100A8 was measured by real time PCR. RESULTS: It was shown in the LP individuals an increased expression of the S100A8 protein in the cutaneous lesions and HMGB-1, TLR-4 and RAGE in the dermis, in parallel to increased level of mRNAs for S100A8 and S100A9 and decreased expression of RAGE. Moerover, increased serum levels of the dimer S100A8 / A9 was detected in patients compared to controls, in contrast to DAMP HMGB1 that revealed similar levels in both groups. The influence of S100A8 in CD8 + T cells and NK cells, was analyzed in PBMC activating with...

Biomarcadores de inflamación subclínica en pacientes infanto-juveniles con diabetes tipo 1 / Subclinical inflammation biomarkers in an infant-juvenile patients with type 1 diabetes

La diabetes tipo 1 (DT1) se asocia a un riesgo incrementado de complicaciones vasculares. Las citoquinas proinflamatorias IL-6, MCP-1 y TNF-α han sido implicadas en el desarrollo de estas complicaciones. El objetivo de este trabajo fue determinar los niveles plasmáticos de IL-6, MCP-1, TNF-α, PCRus y fibrinógeno (Fg) en pacientes infanto-juveniles con DT1 y su asociación con el grado de control glucémico y tiempo de evolución de la enfermedad. Se estudiaron 45 pacientes con DT1 (24 M/21 F), edad 11,2}1,8 años, con tiempo de evolución de la enfermedad de 3,1}3,0 años, sin complicaciones vasculares, que se compararon con 20 sujetos sanos. Se determinaron los niveles plasmáticos de IL-6, MCP-1 y TNF-α, Fg, PCRus, recuento de leucocitos, glucemia en ayunas y HbA1c. Se descartó la presencia de retinopatía y nefropatía. Los datos fueron analizados con el programa SPSS 15 para Windows. Los niños diabéticos presentaron niveles mayores de IL-6 (1,10}0,74 vs 0,68}0,19 pg/ml; p=0,005), MCP-1 (130}49 vs 95}18 pg/ml; p=0,02), PCRus (1,02}1,07 vs 0,43}026 mg/l; p=0,007), Fg (299}59 vs 246}18 mg/dl, p=0,0001), respecto de los controles. No se observaron diferencias significativas de TNF-α entre ambos grupos. Al agrupar a los diabéticos según el grado de control glucémico (HbA1c <8% y ≥8%) y el tiempo de evolución de la enfermedad (≤3 y >3 años), no se encontraron diferencias significativas en las moléculas estudiadas. En los diabéticos la HbA1c se correlaciono con IL-6, MCP-1 y PCRus. Estos resultados reflejan un estado proinflamatorio en la población diabética estudiada.

Aspectos inmunológicos de la enfermedad celíaca / Immunological aspects of celiac disease

La enfermedad celíaca (EC) es un trastorno inflamatorio crónico del intestino delgado inducido por la ingestión de gluten de trigo y otras prolaminas de cereales como cebada, centeno o avena. Afecta a las personas con susceptibilidad genética, y se manifiesta por una lesión de la mucosa intestinal (con linfocitosis intraepitelial, pérdida de vellosidades y remodelación tisular), y la presencia de anticuerpos antitransglutaminasa. El modelo patogénico más aceptado se basa en la activación de una respuesta de la inmunidad adaptativa tras la estimulación de linfocitos T CD4+ mediante péptidos de gluten modificados por la enzima transglutaminasa tisular presentados junto a moléculas HLA-DQ2 o DQ8, y la producción de citoquinas y otros mediadores pro inflamatorios. El gluten activa también la inmunidad innata local y los mecanismos de citotoxicidad sobre el epitelio mediados por linfocitos intraepiteliales. Aunque no se conoce bien cuál es el efecto o la implicación patogénica de los anticuerpos específicos de la EC, la disponibilidad de marcadores serológicos e inmunogenéticos como herramientas diagnósticas ha propiciado el avance en el conocimiento de la EC, y la revisión de los criterios diagnósticos, especialmente en los individuos adultos con expresión mínima o atípica de la enfermedad...

Visión panorámica del sistema inmune / Panoramic vision of the inmune system

El sistema inmune media numerosas patologías, por lo que es importante conocer su estructura y funcionamiento. Se clasifica en innato y adquirido. El sistema inmune innato brinda una temprana e inespecífica respuesta contra los microorganismos. El sistema inmune adquirido humoral y celular nos brinda una respuesta específica para diferentes moléculas, posee memoria frente a los antígenos y diversidad para reaccionar a una gran variedad de antígenos.

The immune system mediates numerous pathologies functions por functioning it is important to know its structure and functioning. The immune system is classified into innate and adaptive immunity. The innate immunity provides early and non-specific response against microbes. The adaptive humoral and cellular immunity gives specificy for distinct molecules and has memory to enhance response to antigen and diversity to responde to large variety of antigen

Estrategias de protección pulmonaren cirugía cardiovascular / Lung protection strategies in cardiovascular surgery

Antecedentes: durante la ventilación mecánica las estructuras pulmonares están sometidasa fuerzas complejas e inusuales que son particularmente relevantes en la incitacióndel daño pulmonar. Las respuestas inflamatoria pulmonar y sistémica secundarias en el pacientede cirugía mayor y cardiovascular, es generada en gran parte por la sobredistención/compresión dela células alveolares y de los bronquiolos terminales, los flujos turbulentos de gases o fluidos al interiordel lumen bronquial, los fenómenos de isquemia/reperfusión pulmonar luego de la circulaciónextracorpórea y la consecuente activación del complemento, citoquinas y demás respuestas celularespro-inflamatorias.Métodos: se realizó una revisión de la literatura disponible en múltiples bases indexadas de literaturamédica (PubMed, ScieLO, Hinari y Cochrane) desde enero de 1990 hasta diciembre de2011, sobre estudios clínicos aleatorizados, estudios retrospectivos y guías de práctica clínica, queidentificaran las principales estrategias para ventilación mecánica protectora (VMP) en pacientes decirugía cardiovascular y cirugía mayor. Resultados y conclusiones: el modo óptimo de soporteventilatorio en cirugía cardiovascular y cirugíamayor continua siendo objeto de debate. La evidenciaexperimental y clínica sugiere que los bajos volúmenescorrientes, bajas presiones al final de la inspiración yla instauración de alta presión al final de la espiraciónpodrían reducir la injuria pulmonar asociada a la ventilaciónmecánica. Algunas recomendaciones actualescomo la utilización de volúmenes corrientes de 6 a 8 ml/kgdel peso ideal, han sido extractadas de grandes estudiosretrospectivos realizados en otro tipo de poblaciones.

Background: Lung structures are exposed tocomplex and unusual forces during mechanicalventilation. This phenomena is particularly relevantto induce lung damage due to overdistension,generation of turbulent flows of gases andfluids into the alveolar and peripheral bronchiallumen, induction of ischemia-reperfusion lesionand inmunological activation, which are greatlyresponsible of the secondary systematic inflammatoryresponse.Methods: A search of available medical literaturerelated to protective mechanical ventilation(PMV) in cardiovascular surgery and major surgerywas conducted using different medical databases(PubMed/MEDline, SciELO, Hinari andCochrane). RCTs, retrospective clinical studies,revision articles, case series, cases and controlsstudies, and clinical guides were reviewed.Results and conclusions: The optimal way forventilatory support in cardiovascular and majorsurgery is object to debate. Experimental evidencesuggests that ventilation with low tidalvolume, lowers pressure at the end of inspiration,and high pressure at the end of expiration,can reduce lung injury associated to ventilation.It was therefore recommended to use currentvolumes from 6 to 8 ml/Kg of the ideal weightand was defined by the Acute Respiratory DistressSyndrome Net as “protective pulmonaryventilation”. Based on studies carried out, thereis no convincing evidence that protective mechanicalventilation (Low VT with PEEP) lowersthe release of cytokines, transfusion needs, mechanicalventilation times, improve post-surgerypulmonary function or a decrease in mortality,intensive care or hospital stay compared to theconventional ventilation in cardiovascular ormajor surgery.

Polimorfismo genetico para lainterleukina-1ß como modulador de losprocesos de reabsorción ósea / Genetic polymorphism for interleukin-1ß as a modulator of boneresorption processes

En general, los factores genéticos influencian la respuesta inflamatoria e inmune, haciendo que losindividuos puedan responder de manera diferente a un mismo cambio en el ambiente. Así, el perfil genéticode cada individuo modula o influencia esa respuesta. La interleukina 1ß (IL-1 ß) es un potente activadorde la actividad osteoclástica y una variación genética de la proteína, conocida como polimorfismo, puedeaumentar su efecto, lo que afectaría negativamente el pronóstico en los tratamientos odontológicos. Elestudio de los polimorfismos genéticos de las interleuquinas se ha convertido en tema de gran interésy debate académico en diferentes ramas de la salud, debido a la importancia que parecen tener comomoduladores de los procesos de reabsorción ósea. Porque los polimorfismos genéticos pueden ayudar a explicar las diferentes respuestas al tratamiento endodóntico en diferentes pacientes. El propósito de estarevisión es actualizar la información previamente publicada relacionada con los polimorfismos genéticos.

Genetic factors influence inflammatory and immune responses in general, and individuals may responddifferently to common environmental challenges. Therefore the genetic profile for every individual moduleor influence that response. Interleukin 1ß (IL-1 ß) is a potent activator of osteoclastic activity and geneticvariation of the protein, known as polymorphism, may increase its effect, which would negatively affectthe prognosis of dental treatment. The study of genetic polymorphisms of interleukins has become atopic of great interest and academic debate in different areas of health, given the importance they seemto have as modulators of bone resorption processes. Because of the genetic polymorphisms might helpexplain the different responses to endodontic treatment in different patients, the purpose of this literaturereview is to update previously published information regarding genetic polymorphism.

Papel de las células nkt invariantes en la respuesta inmune anti-viral: [revisión] / Role of invariant nkt cells in the anti-viral immune response: [review]

Las células T asesinas naturales con receptor de células T invariante y restringidas por la molécula CD1d (iNKT) son un subgrupo de linfocitos con potente actividad inmunorreguladora; su respuesta casi inmediata y la capacidad de producir citoquinas tanto Th1 como Th2 son factores determinantes en el desarrollo de la respuesta inmune innata y adaptativa. El papel fisiológico de las células iNKT se ha documentado ampliamente en la respuesta anti-tumoral, el desarrollo de la tolerancia en los órganos inmunoprivilegiados y el control de las reacciones autoinmunes. A pesar de la demostrada potencia inmunomoduladora de las células iNKT, hasta el momento se conoce poco de su acción en la respuesta inmune anti-infecciosa, en particular en el ser humano y contra los virus patógenos. Este artículo sintetiza los resultados de una búsqueda en las principales bases de datos biomédicas (Pubmed, Medline y OVID), e incluye los estudios realizados para caracterizar estas células y evaluar su papel en la interacción del hospedero con los virus. Las células iNKT participan en la respuesta inmune antiviral, aunque de una manera diferente según el tipo de virus; incluso, podrían estar comprometidas en los daños mediados por mecanismos inmunes. En el ser humano, las células iNKT son aparentemente esenciales en la respuesta inmune contra el virus Varicela Zoster, mientras que todavía hay controversia sobre su función en el control de otros virus. Los modelos animales han aportado las primeras evidencias sobre el potencial de la manipulación terapéutica específica de este subgrupo de linfocitos.

Natural killer T cells with an invariant T-cell receptor and restricted by CD1d (iNKT) are a subgroup of lymphocytes with a very strong immunoregulatory potential; their quick response and their ability to produce Th1 and Th2 cytokines are determinant factors that influence the development of innate and adaptive immune responses. The physiological role of iNKT cells has been well documented in anti-tumor immune responses, the development of tolerance in immune-privileged organs and the control of autoimmune diseases. Despite the fact that the immunoregulatory potential of these cells has been well documented, less is known regarding their role in the immune response against infectious agents, in particular to human pathogenic viruses. This paper synthesizes the search in the most important biomedical data bases (Pubmed, Medline, OVID), including studies on the phenotypic characterization of these cells and functional studies that evaluated their role in the interaction between hosts and viruses. iNKT cells have a heterogeneous participation during the anti-viral immune responses, depending on the type of virus; indeed, in some instances the iNKT-cell responses can be involved in the tissue damage associated to the anti-viral responses. In humans, iNKT cells are apparently essential for an effective immune response against Varicella Zoster virus, while it is still controversial their role in the control of other viral infections. Studies in animal models have shown the first evidences on the therapeutic potential of this lymphocyte subpopulation.