RIP-beta(2)-microglobulin transgene expression restores insulitis, but not diabetes, in beta(2)-microglobulin(null) nonobese diabetic mice
- Author(s)
- Kay, TWH; Parker, JL; Stephens, LA; Thomas, HE; Allison, J;
- Details
- Publication Year 1996-10-15,Volume 157,Issue #8,Page 3688-3693
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- beta(2)m-deficient nonobese diabetic (NOD beta(2)m(null)) do not develop insulitis or diabetes. Expression of a beta(2)m transgene controlled by the rat insulin promoter (RIP-beta(2)m) in NOD beta(2)m(null) mice resulted in reconstitution of IFN-gamma-inducible cell surface MHC class I protein on pancreatic beta-cells. These mice developed insulitis, but did not develop diabetes, Transfer of T cells from diabetic NOD mice to NOD beta(2)m(null) recipients resulted in insulitis, which took several months to progress to diabetes. In contrast, transgenic RIP-beta(2)m/NOD beta(2)m(null) mice with islet MHC class I reconstitution developed diabetes rapidly after transfer of diabetic NOD spleen cells. Administration of cyclophosphamide, which accelerates diabetes in NOD mice, resulted in 43% of RIP-beta(2)m/NOD beta(2)m(null) mice becoming diabetic compared with 75% of wild-type mice and 0% of NOD beta(2)m(null) mice. Acceleration of diabetes by cyclophosphamide was prevented by anti-CD8 mAb treatment. FAGS analysis of peripheral blood and lymphoid organs from transgene-bearing animals did not show an increase in;the number of CD8(+) T cells compared with that in NOD beta(2)m(null) mice. In summary, beta-cell expression of beta(2)m in NOD beta(2)m(null) mice resulted in a return of insulitis, but not spontaneous diabetes, These studies demonstrate that beta(2)m and cell surface MHC class I expression on beta-cells are essential for the initiation of diabetes in the NOD mouse and further confirm that efficient progression to diabetes requires both CD4(+) and CD8(+) T cells.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- MHC CLASS-I; BETA-CELL DESTRUCTION; BETA-2-MICROGLOBULIN DEFICIENT MICE; CD8+ T-CELLS; NOD MOUSE; INTERFERON-GAMMA; LYMPHOCYTES-T; VIRUS-INFECTION; VIRAL-ANTIGEN; TOLERANCE
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Creation Date: 1996-10-15 12:00:00