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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Abstract

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
Additional Information:	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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