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Diabetes, Vol 43, Issue 3 500-504, Copyright © 1994 by American Diabetes Association

ARTICLES

Beta 2-microglobulin-deficient NOD mice do not develop insulitis or diabetes

LS Wicker, EH Leiter, JA Todd, RJ Renjilian, E Peterson, PA Fischer, PL Podolin, M Zijlstra, R Jaenisch and LB Peterson
Department of Autoimmune Diseases Research, Merck Research Laboratories, Rahway, New Jersey 07065-0900.

The role of CD8+ T-cells in the development of diabetes in the nonobese diabetic (NOD) mouse remains controversial. Although it is widely agreed that class II-restricted CD4+ T-cells are essential for the development of diabetes in the NOD model, some studies have suggested that CD8+ T-cells are not required for beta-cell destruction. To assess the contribution of CD8+ T-cells to diabetes, we have developed a class of NOD mouse that lacks expression of beta 2-microglobulin (NOD-B2mnull). NOD-B2mnull mice, which lack both class I expression and CD8+ T-cells in the periphery, not only failed to develop diabetes but were completely devoid of insulitis. These results demonstrate an essential role for CD8+ T-cells in the initiation of the autoimmune response to beta-cells in the NOD mouse.
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