In vivo diabetogenic action of CD4+ T lymphocytes requires Fas expression and is independent of IL-1 and IL-18

✍ Scribed by Li Wen; Elizabeth A. Green; Thomas Stratmann; Anaïs Panosa; Ramon Gomis; Elizabeth E. Eynon; Richard A. Flavell; Jovita A. Mezquita; Conchi Mora

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 249 KB
• Volume: 41
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.201041216

✦ Synopsis

Abstract

CD4^+^ T lymphocytes are required to induce spontaneous autoimmune diabetes in the NOD mouse. Since pancreatic β cells upregulate Fas expression upon exposure to pro‐inflammatory cytokines, we studied whether the diabetogenic action of CD4^+^ T lymphocytes depends on Fas expression on target cells. We assayed the diabetogenic capacity of NOD spleen CD4^+^ T lymphocytes when adoptively transferred into a NOD mouse model combining: (i) Fas‐deficiency, (ii) FasL‐deficiency, and (iii) SCID mutation. We found that CD4^+^ T lymphocytes require Fas expression in the recipients' target cells to induce diabetes. IL‐1β has been described as a key cytokine involved in Fas upregulation on mouse β cells. We addressed whether CD4^+^ T cells require IL‐1β to induce diabetes. We also studied spontaneous diabetes onset in NOD/IL‐1 converting enzyme‐deficient mice, in NOD/IL‐1β‐deficient mice, and CD4^+^ T‐cell adoptively transferred diabetes into NOD/SCID IL‐1β‐deficient mice. Neither IL‐1β nor IL‐18 are required for either spontaneous or CD4^+^ T‐cell adoptively transferred diabetes. We conclude that CD4^+^ T‐cell‐mediated β‐cell damage in autoimmune diabetes depends on Fas expression, but not on IL‐1β unveiling the existing redundancy regarding the cytokines involved in Fas upregulation on NOD β cells in vivo.