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

Research output: Contribution to journalArticle

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 2004
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Subudhi, S. K., Zhou, P., Yerian, L. M., Chin, R. K., Lo, J. C., Anders, R. A., Sun, Y., Chen, L., Wang, Y., Alegre, M. L., & Fu, Y. X. (2004). Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection. Journal of Clinical Investigation, 113(5), 694-700. https://doi.org/10.1172/JCI200419210