Gibbons, R.

Abstract Studies from cancer and chronic infections show that B7-H1 (PD-L1) engagement with its receptor PD-1 enhances apoptosis of effector T cells. It is not clear how B7-H1 regulates T cell apoptosis and the subsequent impact of B7-H1 on T cell memory generation. In immunized B7-H1 deficient mice we observed increased expansion of effector CD8 T cells and delayed T cell contraction followed by protective CD8 T cell memory capable of completely rejecting tumor metastases in lung tissue. Intracellular staining revealed that antigen-primed CD8 T cells in B7-H1 deficient mice express lower levels of the pro-apoptotic molecule Bim. Injection of B7-H1 or PD-1 blocking antibody into immunized mice reduced Bim levels in effector CD8 T cells. In vitro studies show that engagement of activated CD8 T cells by plate-bound B7-H1 fusion protein led to increased cell death and higher levels of Bim expression. Our results suggest that B7-H1 may negatively regulate CD8 T cell memory by enhancing the depletion of effector CD8 T cells through up-regulation of Bim. Our findings would provide a new strategy to target B7-H1 signaling in effector CD8 T cells to achieve protective immunity in the treatment of cancer and infectious diseases.