دورية أكاديمية
Interferon-γ Limits Diabetogenic CD8(+) T-Cell Effector Responses in Type 1 Diabetes.
| العنوان: | Interferon-γ Limits Diabetogenic CD8(+) T-Cell Effector Responses in Type 1 Diabetes. |
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| المؤلفون: | Driver, John P, Racine, Jeremy, Ye, Cheng, Lamont, Deanna J, Newby, Brittney N, Leeth, Caroline M, Chapman, Harold D, Brusko, Todd M, Chen, Yi-Guang, Mathews, Clayton E, Serreze, David V |
| المصدر: | Faculty Research 2017 |
| بيانات النشر: | The Mouseion at the JAXlibrary |
| سنة النشر: | 2017 |
| المجموعة: | The Jackson Laboratory: The Mouseion at the JAXlibrary |
| مصطلحات موضوعية: | Life Sciences, Medicine and Health Sciences |
| الوصف: | Type 1 diabetes development in the NOD mouse model is widely reported to be dependent on high-level production by autoreactive CD4(+) and CD8(+) T cells of interferon-γ (IFN-γ), generally considered a proinflammatory cytokine. However, IFN-γ can also participate in tolerance-induction pathways, indicating it is not solely proinflammatory. This study addresses how IFN-γ can suppress activation of diabetogenic CD8(+) T cells. CD8(+) T cells transgenically expressing the diabetogenic AI4 T-cell receptor adoptively transferred disease to otherwise unmanipulated NOD.IFN-γ(null) , but not standard NOD, mice. AI4 T cells only underwent vigorous intrasplenic proliferation in NOD.IFN-γ(null) recipients. Disease-protective IFN-γ could be derived from any lymphocyte source and suppressed diabetogenic CD8(+) T-cell responses both directly and through an intermediary nonlymphoid cell population. Suppression was not dependent on regulatory T cells, but was associated with increased inhibitory STAT1 to STAT4 expression levels in pathogenic AI4 T cells. Importantly, IFN-γ exposure during activation reduced the cytotoxicity of human-origin type 1 diabetes-relevant autoreactive CD8(+) T cells. Collectively, these results indicate that rather than marking the most proinflammatory lymphocytes in diabetes development, IFN-γ production could represent an attempted limitation of pathogenic CD8(+) T-cell activation. Thus, great care should be taken when designing possible diabetic intervention approaches modulating IFN-γ production. Diabetes 2017 Mar; 66(3):710-721. |
| نوع الوثيقة: | text |
| اللغة: | unknown |
| العلاقة: | https://mouseion.jax.org/stfb2017/40Test |
| DOI: | 10.2337/db16-0846 |
| الإتاحة: | https://doi.org/10.2337/db16-0846Test https://mouseion.jax.org/stfb2017/40Test |
| رقم الانضمام: | edsbas.8AF17278 |
| قاعدة البيانات: | BASE |
| DOI: | 10.2337/db16-0846 |
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