PREVENTION OF INSULITIS AND DIABETES IN BETA(2)-MICROGLOBULIN-DEFICIENT NONOBESE DIABETIC MICE

beta(2)-Microglobulin (beta(2)m)-deficient non-obese diabetic (NOD) mice were established by crossing beta(2)m-deficient 129/Sv mice with NOD mice, and used to examine the possible involvement of MHC class I molecules and CD8(+) T cells in the development of insulitis and diabetes. In these mice, MHC class I molecules were not expressed, resulting in no generation of CD8(+) T cells. None of eight lines of beta(2)m-deficient NOD mice (-/-) established developed overt diabetes by 32 weeks, while control littermates (+/+) became diabetic by 22 weeks. histological studies showed no significant lymphocyte infiltration of the islets (insulitis score: 0.03 +/- 0.03) in any of the beta(2)m-deficient NOD mice (-/-) compared with littermate NOD mice (+/+) with overt insulitis (1.42 +/- 0.28). These findings support the notion that the expression of MHC class I molecules and/or CD8(+) T cells plays an essential role in the infiltration of CD4(+) T cells in islets as well as the development of diabetes in NOD mice.