title: B7-H1 limits the entry of effector CD8(+) T cells to the memory pool by upregulating Bim.
abstract: Protective T‑cell immunity against cancer and infections is dependent on the generation of a durable effector and memory T‑cell pool. Studies from cancer and chronic infections reveal that B7-H1 (PD-L1) engagement with its receptor PD-1 promotes apoptosis of effector T cells. It is not clear how B7-H1 regulates T‑cell apoptosis and the subsequent impact of B7-H1 on the generation of memory T cells. In immunized B7-H1-deficient mice, we detected an increased expansion of effector CD8(+) T cells and a delayed T‑cell contraction followed by the emergence of a protective CD8(+) T‑cell memory capable of completely rejecting tumor metastases in the lung. Intracellular staining revealed that antigen-primed CD8(+) T cells in B7-H1-deficient mice express lower levels of the pro-apoptotic molecule Bim. The engagement of activated CD8(+) T cells by a plate-bound B7-H1 fusion protein led to the upregulation of Bim and increased cell death. Assays based on blocking antibodies determined that both PD-1 and CD80 are involved in the B7-H1-mediated regulation of Bim in activated CD8(+) T cells. Our results suggest that B7-H1 may negatively regulate CD8(+) T‑cell memory by enhancing the depletion of effector CD8(+) T cells through the upregulation of Bim. Our findings may provide a new strategy for targeting B7-H1 signaling in effector CD8(+) T cells to achieve protective antitumor memory responses.
authors.affiliation: Department of Immunology; College of Medicine; Mayo Clinic; Rochester, MN USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Gibbons
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Vesna
authors.initials: V
authors.lastname: Pulko
authors.forename: Susan M
authors.initials: SM
authors.lastname: Harrington
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Krco
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Kwon
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong