Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection

Sumit K. Subudhi, Ping Zhou, Lisa M. Yerian, Robert K. Chin, James C. Lo, Robert A. Anders, Yonglian Sun, Lieping Chen, Yang Wang, Maria Luisa Alegre, Yang Xin Fu

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)694-700
Number of pages7
JournalJournal of Clinical Investigation
Volume113
Issue number5
DOIs
StatePublished - Mar 1 2004

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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.

Research output: Contribution to journalArticle