科研之友
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摘要
B7x (B7-H4 or B7S1) is the seventh member of the B7 family, and its in vivo function remains largely unknown. Despite new genetic data linking the B7x gene with autoimmune diseases, how exactly it contributes to peripheral tolerance and autoimmunity is unclear. In this study, we showed that B7x protein was not detected on APCs or T cells in both human and mice, which is unique in the B7 family. Because B7x protein is expressed in some peripheral cells such as pancreatic beta cells, we used a CD8 T cell-mediated diabetes model (AI4 alpha beta) in which CD8 T cells recognize an endogenous self-Ag, and found that mice lacking B7x developed more severe diabetes than control AI4 alpha beta mice. Conversely, mice overexpressing B7x in the beta cells (Rip-B7xAI4 alpha beta) were diabetes free. Furthermore, adoptive transfer of effector AI4 alpha beta CD8 T cells induced diabetes in control mice, but not in Rip-B7xAI4 alpha beta mice. Mechanistic studies revealed that pathogenic effector CD8 T cells were capable of migrating to the pancreas but failed to robustly destroy tissue when encountering local B7x in Rip-B7xAI4 alpha beta mice. Although AI4 alpha beta CD8 T cells in Rip-B7xAI4 alpha beta and AI4 alpha beta mice showed similar cytotoxic function, cell death, and global gene expression profiles, these cells had greater proliferation in AI4 alpha beta mice than in RIP-B7xAI4 alpha beta mice. These results suggest that B7x in nonlymphoid organs prevents peripheral autoimmunity partially through inhibiting proliferation of tissue-specific CD8 T cells, and that local overexpression of B7x on pancreatic b cells is sufficient to abolish CD8 T cell-induced diabetes. The Journal of Immunology, 2012, 189: 4165-4174.
- 出版日期2012-10-15
