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Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection
Sumit K. Subudhi, … , Maria-Luisa Alegre, Yang-Xin Fu
Sumit K. Subudhi, … , Maria-Luisa Alegre, Yang-Xin Fu
Published March 1, 2004
Citation Information: J Clin Invest. 2004;113(5):694-700. https://doi.org/10.1172/JCI19210.
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Article Autoimmunity

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

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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.

Authors

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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Figure 1

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Generation of RIP.B7-H1 transgenic mice. (A) A schematic of the RIP–muri...
Generation of RIP.B7-H1 transgenic mice. (A) A schematic of the RIP–murine B7-H1 hybrid gene. (B) Southern blot analysis of mouse genomic DNA digested with BamHI and hybridized with a full-length murine B7-H1 probe. (C) Immunofluorescence staining of insulin (green) and murine B7-H1 (red) in pancreata (original magnification, ×40) from C57BL/6 and RIP.B7-H1 mice.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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