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

Rachel M. Gibbons, Xin Liu, Vesna Pulko, Susan M. Harrington, Christopher J. Krco, Eugene D. Kwon, Haidong Dong

Research output: Contribution to journalArticle

30 Scopus citations

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-H 1 (PD-L1) engagement with its receptor PD-1 promotes apoptosis of effector T cells. It is not clear how B7-H 1 regulates T-cell apoptosis and the subsequent impact of B7-H 1 on the generation of memory T cells. In immunized B7-H 1-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-H 1-deficient mice express lower levels of the pro-apoptotic molecule Bim. The engagement of activated CD8+ T cells by a plate-bound B7-H 1 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-H 1-mediated regulation of Bim in activated CD8+ T cells. Our results suggest that B7-H 1 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-H 1 signaling in effector CD8+ T cells to achieve protective antitumor memory responses.

Original languageEnglish (US)
Pages (from-to)1061-1073
Number of pages13
JournalOncoImmunology
Volume1
Issue number7
DOIs
StatePublished - 2012

Keywords

  • Apoptosis
  • B7-H1
  • Metastasis
  • PD-1
  • Tumor immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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