BETA-2-MICROGLOBULIN-DEFICIENT NOD MICE DO NOT DEVELOP INSULITIS OR DIABETES

The role of CD8(+) T-cells in the development of diabetes in the nonob ese diabetic (NOD) mouse remains controversial. Although it is widely agreed that class II-restricted CD4(+) T-cells are essential for the d evelopment of diabetes in the NOD model, some studies have suggested t hat CD8(+) T-cells are not required for beta-cell destruction. To asse ss the contribution of CD8(+) T-cells to diabetes, we have developed a class of NOD mouse that lacks expression of beta 2-microglobulin (NOD -B2m(null)). NOD-B2m(null) mice, which lack both class I expression an d 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.