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Role of PD-1 during effector CD8 T cell differentiation
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Role of PD-1 during effector CD8 T cell differentiation
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Role of PD-1 during effector CD8 T cell differentiation
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Journal Article
Role of PD-1 during effector CD8 T cell differentiation
2018
Overview
PD-1 (programmed cell death-1) is the central inhibitory receptor regulating CD8 T cell exhaustion during chronic viral infection and cancer. Interestingly, PD-1 is also expressed transiently by activated CD8 T cells during acute viral infection, but the role of PD-1 in modulating T cell effector differentiation and function is not well defined. To address this question, we examined the expression kinetics and role of PD-1 during acute lymphocytic choriomeningitis virus (LCMV) infection of mice. PD-1 was rapidly up-regulated in vivo upon activation of naive virus-specific CD8 T cells within 24 h after LCMV infection and in less than 4 h after peptide injection, well before any cell division had occurred. This rapid PD-1 expression by CD8 T cells was driven predominantly by antigen receptor signaling since infection with a LCMV strain with a mutation in the CD8 T cell epitope did not result in the increase of PD-1 on antigen-specific CD8 T cells. Blockade of the PD-1 pathway using anti–PD-L1 or anti–PD-1 antibodies during the early phase of acute LCMV infection increased mTOR signaling and granzyme B expression in virus-specific CD8 T cells and resulted in faster clearance of the infection. These results show that PD-1 plays an inhibitory role during the naive-to-effector CD8 T cell transition and that the PD-1 pathway can also be modulated at this stage of T cell differentiation. These findings have implications for developing therapeutic vaccination strategies in combination with PD-1 blockade.
Publisher
National Academy of Sciences
Subject
/ Cancer
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - pathology
/ Cell Differentiation - genetics
/ Cell Differentiation - immunology
/ Epitopes
/ Female
/ Lymphocytic Choriomeningitis - genetics
/ Lymphocytic Choriomeningitis - immunology
/ Lymphocytic choriomeningitis virus - immunology
/ Mice
/ Programmed Cell Death 1 Receptor - genetics
/ Programmed Cell Death 1 Receptor - immunology
/ Receptors, Antigen, T-Cell - genetics
/ Receptors, Antigen, T-Cell - immunology
/ Studies
/ Viruses
