β2-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 β-cell destruction. To assess the contribution of CD8⁺ T-cells to diabetes, we have developed a class of NOD mouse that lacks expression of βxs2-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 β-cells in the NOD mouse.