THE ROLE OF LYMPHOCYTE SUBSETS IN ACCELERATED DIABETES IN NONOBESE DIABETIC RAT INSULIN PROMOTER B7-1 (NOD-RIP-B7-1) MICE

B7-1 transgene expression on the pancreatic islets in nonobese diabeti c (NOD) mice leads to accelerated diabetes, with >50% of animals devel oping diabetes before 12 wk of age. The expression of B7-1 directly on the pancreatic beta cells, which do not normally express costimulator molecules, converts the cells into effective antigen-presenting cells leading to an intensified autoimmune attack. The pancreatic islet inf iltrate in diabetic mice consists of CD8 T cells, CD4 T cells, and B c ells, similar to diabetic nontransgenic NOD mice. To elucidate the rel ative importance of each of the subsets of cells, the NOD-rat insulin promoter (RIP)-B7-1 animals were crossed with NOD.beta 2microglobulin -/- mice which lack major histocompatibility complex class I molecules and are deficient in peripheral CD8 T cells, NOD.CD4 -/- mice which l ack T cells expressing CD4, and NOD.mu MT -/- mice which lack B220-pos itive B cells. These experiments showed that both CD4 and CD8 T cells were necessary for the accelerated onset of diabetes, but that B cells , which are needed for diabetes to occur in normal NOD mice, are not r equired. It is possible that B lymphocytes play an important role in t he provision of costimulation in NOD mice which is unnecessary in the NOD-RIP-B7-1 transgenic mice.