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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 4

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B7-H1 expression in the pancreatic islets promotes CD8+ T cell priming a...
B7-H1 expression in the pancreatic islets promotes CD8+ T cell priming and autoimmune diabetes induction. (A) OT-I T cells (2 × 106) were adoptively transferred into RIP.mOVA and RIP.B7-H1/mOVA mice. Incidence of diabetes was evaluated at daily intervals. (B) Pancreata were stained with H&E, and individual islets from three mice per group were assigned scores for insulitis at the time of diabetes onset (RIP.B7-H1/mOVA mice) or day 22 after transfer for those mice that did not develop diabetes. (C) H&E staining of pancreata from RIP.mOVA and RIP.B7-H1/mOVA mice before and after transfer of 2 × 106 OT-I T cells. Original magnifications: top panels, ×20; bottom panels, ×40. (D) CFSE-labeled OT-I T cells (2 × 106) were adoptively transferred into RIP.mOVA and RIP.B7-H1/mOVA mice. Then, 42 hours later, the pancreatic draining lymph node cells were analyzed by flow cytometry. The numbers indicate the percentage of dividing OT-I T cells. (E) CFSE-labeled OT-I T cells (2 × 106) were adoptively transferred into RIP.B7-H1/mOVA mice. At the time of transfer, the mice were treated with 100 μg hamster IgG (top panel) or mAb to mouse PD-1 (bottom panel). Then, 42 hours later, the pancreatic draining lymph node cells were analyzed by flow cytometry. The numbers indicate the percentage of dividing OT-I T cells. Each of the experiments was repeated at least three times.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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