Some new members of the B7/CD28 families were discovered over the last several years and their functions in vivo need to be elucidated. We show that B7x (B7-H4 or B7S1) was expressed in pancreatic b cells but not in immune cells. Using a CD8 T cell-mediated diabetes model, we demonstrate that mice lacking B7x developed more severe diabetes than the control, conversely mice overexpressing B7x in b cells were diabetes free. Pathogenically effector CD8 T cells were capable of migrating to the pancreas but failed to kill target cells and destroy tissue when encountering local B7x. In response to the local B7x these CD8 T cells achieved an overlap yet distinct gene-expression profile from anergic or exhausted CD8 T cells. Our findings reveal that B7x in the periphery abrogates CD8 T cell-mediated tissue destruction. B7-H1 (PD-L1) is widely expressed in immune cells and is important in the coinhibition of T cell function via binding its receptor PD-1. We show that both human and mice intestinal epithelium expressed B7-H1 and mice deficient for B7-H1 were highly susceptible to gut injury and associated mortality and morbidity. Defective B7-H1 led to loss of epithelial integrity and systemic dispersion of commensal bacteria during intestinal inflammation. B7-H1 expressed on parenchymal cells but not on hematopoietic cells controlled intestinal inflammation, which was not dependent on PD-1, B7-1(CD80), and the adaptive immunity.
- Copyright © 2011 by The American Association of Immunologists, Inc.