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 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-B2m(null)). NOD-B2m(null) 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.