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J Clin Invest. 2004 Mar;113(5):694-700.

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

Author information

1
Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.

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 beta cells. Surprisingly, we observed accelerated rejection of transplanted allogeneic B7-H1-expressing islet beta 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.

PMID:
14991067
PMCID:
PMC351315
DOI:
10.1172/JCI19210
[Indexed for MEDLINE]
Free PMC Article

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