1. B7x in the Periphery Abrogates Pancreas-Specific Damage Mediated by Self-reactive CD8 T Cells.
- Author
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Lee, Jun Sik, Scandiuzzi, Lisa, Ray, Anjana, Wei, Joyce, Hofmeyer, Kimberly A., Abadi, Yael M., Loke, P'ng, Lin, Juan, Yuan, Jianda, Serreze, David Y., Allison, James P., and Zang, Xingxing
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CD8 antigen , *T cells , *AUTOIMMUNE diseases , *IMMUNOLOGICAL tolerance , *PANCREATIC beta cells , *LABORATORY mice , *CELLULAR immunity , *GENE expression - Abstract
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 β 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 β cells, we used a CD8 T cell-mediated diabetes model (A14αβP) in which CD8 T cells recognize an endogenous self-Ag, and found that mice lacking B7x developed more severe diabetes than control AI4aP mice. Conversely, mice overexpressing B7x in the β cells (Rip-B7xA14αβ) were diabetes free. Furthermore, adoptive transfer of effector A14αβ CD8 T cells induced diabetes in control mice, but not in Rip-B7xA14αβ 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-B7xA14αβ mice. Although A14αβ CD8 T cells in Rip-B7xA14αβ and A14αβ mice showed similar cytotoxic function, cell death, and global gene expression profiles, these cells had greater proliferation in A14αβ mice than in RIP-B7xAαβ mice. These results suggest that B7x in nonlymphoid organs prevents peripheral autoim-munity partially through inhibiting proliferation of tissue-specific CD8 T cells, and that local overexpression of B7x on pancreatic β cells is sufficient to abolish CD8 T cell-induced diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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