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Section of Endocrinology, and the Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510
B7-1 transgene expression on the pancreatic islets in nonobese diabetic (NOD) mice leads to accelerated diabetes, with >50% of animals developing diabetes before 12 wk of age. The expression of B7-1 directly on the pancreatic β 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 infiltrate in diabetic mice consists of CD8 T cells, CD4 T cells, and B cells, similar to diabetic nontransgenic NOD mice. To elucidate the relative importance of each of the subsets of cells, the NOD–rat insulin promoter (RIP)-B7-1 animals were crossed with NOD.β2microglobulin –/– mice which lack major histocompatibility complex class I molecules and are deficient in peripheral CD8 T cells, NOD.CD4 –/– mice which lack T cells expressing CD4, and NOD.µMT –/– mice which lack B220-positive 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 required. It is possible that B lymphocytes play an important role in the provision of costimulation in NOD mice which is unnecessary in the NOD-RIP-B7-1 transgenic mice.
Key Words: nonobese diabetic mice • rat insulin promoter–B7-1 transgene • accelerated diabetes • T cells • B cells
Abbreviations used: β2m, β2microglobulin; NOD, nonobese diabetic; RIP, rat insulin promoter.
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