B7-H1 limits the entry of effector CD8+ T cells to the memory pool by upregulating Bim

• Published in: Oncoimmunology Vol. 1; no. 7; pp. 1061 - 1073
• Main Authors: Gibbons, Rachel M, Liu, Xin, Pulko, Vesna, Harrington, Susan M, Krco, Christopher J, Kwon, Eugene D, Dong, Haidong
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-10-2012; Landes Bioscience
• Subjects: apoptosis; B7-H1; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cycle; Landes; metastasis; Organogenesis; PD-1; Proteins; Research Paper; tumor immunotherapy
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.4161/onci.20850

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.