Fas/Fas ligand interactions play an essential role in the initiation of murine autoimmune diabetes

Nakayama, Maki, Nagata, Masao, Yasuda, Hisafumi, Arisawa, Kenji, Kotani, Reiko, Yamada, Katsumi, Chowdhury, Shahead Ali, Chakrabarty, Sagarika, Jin, Zhen Zi, Yagita, Hideo, Yokono, Koichi, and Kasuga, Masato (2002) Fas/Fas ligand interactions play an essential role in the initiation of murine autoimmune diabetes. Diabetes, 51 (5). pp. 1391-1397.

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Apoptosis via Fas/Fas ligand (FasL) interactions has been proposed to be a major T-cell-mediated effector mechanism in autoimmune diabetes. To elucidate the role of Fas/FasL interactions in NOD diabetes, the effects of neutralizing anti-FasL antibody on autoimmune responses were evaluated. Islet-specific CD8+ and CD4+ T-cells expressed FasL upon activation and mediated FasL-dependent cytotoxicity against Fas-expressing target cells in vitro, although their cytotoxicity against islet cells was not blocked by anti-FasL antibody. Moreover, administration of anti-FasL antibody failed to inhibit diabetes in vivo in the CD8+ T-cell adoptive transfer model. On the other hand, blockade of Fas/FasL interactions significantly inhibited CD4+ T-cell-dependent diabetes in adoptive transfer models. These results suggest a substantial contribution of Fas/FasL interactions to CD4+, but not CD8+, T-cell-mediated destruction of pancreatic ß-cells. When anti-FasL antibody was administered to NOD mice between 5 and 15 weeks of age, the onset of diabetes was slightly delayed but the incidence was not decreased. However, administration of anti-FasL antibody at 2–4 weeks of age completely prevented insulitis and diabetes. These results suggest that Fas/FasL interactions contribute to CD4+ T-cell-mediated ß-cell destruction and play an essential role in the initiation of autoimmune NOD diabetes.

Item ID: 980
Item Type: Article (Research - C1)
ISSN: 1237-9115
Keywords: NOD mice, Fas, FasL, Apoptosis
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Copyright © 2002 by the American Diabetes Association

Date Deposited: 02 Nov 2006
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 0%
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