Invariant NKT Cells Exacerbate Type 1 Diabetes Induced by CD8 T Cells

Griseri, Thibault; Beaudoin, Lucie; Novák, Jan; Mars, Lennart T.; Lepault, Françoise; Liblau, Roland; Lehuen, Agnès

doi:10.4049/jimmunol.175.4.2091

Cited by 30 publications

(22 citation statements)

References 55 publications

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“…In contrast, NKT cells enhanced the activation and expansion of diabetogenic CD8 ϩ T cells, and their differentiation into effector cells producing IFN-␥, exacerbating the development of diabetes (46). Combined with our results, this suggests that NKT cells regulate immune responses in vivo by enhancing or suppressing the activation and proliferation of CD8 ϩ T cells.…”

Section: Discussionsupporting

confidence: 62%

IL-4-Secreting NKT Cells Prevent Hypersensitivity Pneumonitis by Suppressing IFN-γ-Producing Neutrophils

Hwang

Kim

Park

et al. 2006

The Journal of Immunology

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Hypersensitivity pneumonitis (HP) is mediated by Th1 immune response. NKT cells regulate immune responses by modulating the Th1/Th2 balance. Therefore, we postulated that NKT cells play a critical role in the development of the HP by modulating the Th1/Th2 response. To address this issue, we explored the functional roles of NKT cells in Saccharopolyspora rectivirgula (SR)-induced HP. In CD1d−/− mice, the HP was worse in terms of histological changes, hydroxyproline levels, the CD4:CD8 ratio in bronchoalveolar lavage fluid, and SR-specific immune responses than in control mice. CD1d−/− mice showed elevated IFN-γ production in the lung during the HP, and this was produced mainly by Gr-1+ neutrophils. The blockade of IFN-γ in CD1d−/− mice attenuated the HP, whereas the injection of rIFN-γ aggravated it. Moreover, the depletion of Gr-1+ neutrophils reduced CD8+ T cell numbers in bronchoalveolar lavage fluid during the HP. The adoptive transfer of IL-4−/− mouse NKT cells did not attenuate the HP, whereas wild-type or IFN-γ−/− mouse NKT cells suppressed the HP. In conclusion, NKT cells producing IL-4 play a protective role in SR-induced HP by suppressing IFN-γ-producing neutrophils, which induce the activation and proliferation of CD8+ T cells in the lung.

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Section: Discussionsupporting

confidence: 62%

IL-4-Secreting NKT Cells Prevent Hypersensitivity Pneumonitis by Suppressing IFN-γ-Producing Neutrophils

Hwang

Kim

Park

et al. 2006

The Journal of Immunology

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“…Third, NKT cells might be differentially involved in the regulation of the secondary immune response of different subsets of immune effector cells. In this context, Griseri and colleagues (27) showed that adoptive transfer of islet-specific CD8 + T cells into NKT cell-enriched Va14 + transgenic recipients exacerbated type I diabetes. They also showed that NKT cells impaired the differentiation of anti-islet CD4 + T cells into Th1 effector cells, and that eventually the autoreactive CD4 + T cells become anergic (28 …”

Section: Compared With Cd1dmentioning

confidence: 99%

Regulation of Secondary Antigen-Specific CD8+ T-Cell Responses by Natural Killer T Cells

et al. 2009

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The physiologic function of natural killer T (NKT) cells in adaptive immunity remains largely unknown because most studies have used NKT cell agonists. In the present study, the role of NKT cells during the secondary effector phase was investigated separately from the primary immunization phase via adoptive transfer of differentiated effector T cells into naive recipients. We found that secondary antitumor CD8 + T-cell responses were optimal when NKT cells were present. Tumor-specific CD8 + effector T cells responded less strongly to tumor cell challenge in NKT cell-deficient recipients than in recipients with intact NKT cells. NKT cell-mediated enhancement of the secondary antitumor CD8 + T-cell response was concurrent with increased number and activity of tumorspecific CD8 + T cells. These findings provide the first demonstration of a direct role for NKT cells in the regulation of antigen-specific secondary T-cell responses without the use of exogenous NKT cell agonists such as A-galactosylceramide (A-GalCer). Furthermore, forced activation of NKT cells with A-GalCer during the secondary immune response in suboptimally immunized animals enhanced otherwise poor tumor rejection responses. Taken together, our findings strongly emphasize the importance of NKT cells in secondary CD8+ T-cell immune responses. [Cancer Res 2009;69(10):4301-8]

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“…Enquanto muitos autores concordam que as células TNK contribuem para a prevenção das doenças auto-imunes, a exemplo do DM1, pelo menos em modelo de camundongos NOD, nos quais exercem uma complexa regulação da resposta imune (44)(45)(46)(47), outros estudos referem que estas células não interferem com a doença (48) ou que podem contribuir para o agravamento da mesma (49).…”

Section: Hipótese Da Higiene / Mecanismos Regulatórios Da Resposta Imuneunclassified

Controvérsias na associação entre diabetes mellitus tipo 1 e asma

Alves

Diniz

Souza

et al. 2007

Arq Bras Endocrinol Metab

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RESUMOObjetivo: Revisão crítica da literatura sobre a associação entre asma e diabetes mellitus tipo 1 (DM1). Fonte dos dados: Pesquisa bibliográfica na base de dados MEDLINE e LILACS nos últimos vinte anos. Síntese dos dados: Muitos estudos mostram associação inversa entre asma, atopia e o risco de desenvolver DM1. De acordo com a "Hipótese da Higiene", o risco de doenças alérgicas diminui com infecções precoces na infância no sentido de afastar-se do perfil Th2, predominante ao nascimento, em direção ao fenótipo Th1. No entanto, outros trabalhos demonstram associação positiva ou ausência de associação entre DM1 e alergias. Existe a possibilidade de fatores ambientais contribuírem para ocorrência de doenças mediadas por células Th1 e Th2 no mesmo indivíduo, por provável deficiência de mecanismos imunomodulatórios mediados pela interleucina-10 e células regulatórias. Conclusão: As informações sobre a associação inversa entre doenças mediadas por resposta Th1 (por exemplo, DM1), e aquelas mediadas por resposta Th2 (por exemplo, alergias) são conflitantes, requerendo mais estudos para esclarecer esta questão. Objective: Critical review of the literature to investigate the relationship between asthma and type 1 diabetes mellitus (DM1). Source of data: Bibliography search in MEDLINE and LILACS databases in the last twenty years. Summary of data: Several studies demonstrate an inverse relationship between asthma, atopic diseases and the risk to develop DM1. According to the "Hygiene Hypothesis", the risk of allergic diseases decreases with infections early in childhood, towards distance of Th2 profile, common at birth, to the Th1 phenotype. Other articles described lack of association or positive association between DM1 and allergies. There is a possibility of environmental factors interfering in the development of disorders mediated by Th1 and Th2 cells, in the same individual, due to the absence of immunomodulatory mechanisms mediated by interleukin-10 and regulatory cells. Conclusion: The existing information about the inverse association between Th1-mediated diseases (e.g., DM1), and those that are Th2-mediated (e.g., allergies) are conflicting requiring more investigation to explain this question.

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Invariant NKT Cells Exacerbate Type 1 Diabetes Induced by CD8 T Cells

Cited by 30 publications

References 55 publications

IL-4-Secreting NKT Cells Prevent Hypersensitivity Pneumonitis by Suppressing IFN-γ-Producing Neutrophils

IL-4-Secreting NKT Cells Prevent Hypersensitivity Pneumonitis by Suppressing IFN-γ-Producing Neutrophils

Regulation of Secondary Antigen-Specific CD8+ T-Cell Responses by Natural Killer T Cells

Controvérsias na associação entre diabetes mellitus tipo 1 e asma

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