A number of studies have suggested B7-H1, a B7 family member, inhibits T cell responses. Therefore, its expression on nonlymphoid tissues has been proposed to prevent T cell-mediated tissue destruction. To test this hypothesis, we generated transgenic mice that expressed B7-H1 on pancreatic islet β cells. Surprisingly, we observed accelerated rejection of transplanted allogeneic B7-H1-expressing islet β cells. Furthermore, transgenic B7-H1 expression broke immune tolerance, as some of the mice spontaneously developed T cell-dependent autoimmune diabetes. In addition, B7-H1 expression increased CD8+ T cell proliferation and promoted autoimmunity induction in a T cell adoptive transfer model of diabetes. Consistent with these findings, B7-H1.Ig fusion protein augmented naive T cell priming both in vitro and in vivo. Our results demonstrate that B7-H1 can provide positive costimulation for naive T cells to promote allograft rejection and autoimmune disease pathogenesis.
Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection. / Subudhi, Sumit K.; Zhou, Ping; Yerian, Lisa M.; Chin, Robert K.; Lo, James C.; Anders, Robert A.; Sun, Yonglian; Chen, Lieping; Wang, Yang; Alegre, Maria Luisa; Fu, Yang Xin.In: Journal of Clinical Investigation, Vol. 113, No. 5, 01.03.2004, p. 694-700.
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