Abstract
Anti-viral CD8(+) T cell responses involve an initial expansion and effector phase, followed by contraction phase and formation of CD8(+) memory T cells. During this contraction phase, increased surface expression of the negative regulator PD-1 is associated with functional exhaustion of CD8(+) T cells. Although its role in T cell suppression has been established, the importance of PD-1 in the differentiation of CD8(+) T cells remains unclear. In this study, we examine PD-1 expression in relation to viral specificity of CD8(+) T cells against persistent or non-persistent viruses, and further define differentiation phenotypes of CD8(+) T cells by CD27 and CD28 expression. Surprisingly, the inhibitory receptor PD-1 was expressed by Flu-specific CD8(+) T cells in a level comparable to HCMV-and EBV-specific cells. Moreover, in virus-specific CD8(+) T cells, CD127(+)/CD127(-) and CD62L(+)/CD62L(-) cells expressed similar levels of PD-1 molecules. These results suggest that the PD-1/PD-L1 pathway may play a regulatory role in memory T cell subsets in addition to its association with T-cell exhaustion.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antigens, CD / immunology
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Antigens, CD / metabolism*
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Apoptosis Regulatory Proteins / immunology
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Apoptosis Regulatory Proteins / metabolism*
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B7-H1 Antigen
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CD28 Antigens / immunology
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CD28 Antigens / metabolism
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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China
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Cytomegalovirus / immunology
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Female
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Herpesviridae / immunology*
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Herpesvirus 4, Human / immunology
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Humans
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Immunologic Memory
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Influenza A virus / immunology*
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Interleukin-7 Receptor alpha Subunit / immunology
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Interleukin-7 Receptor alpha Subunit / metabolism
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Male
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Phenotype
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Programmed Cell Death 1 Receptor
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
Substances
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Antigens, CD
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Apoptosis Regulatory Proteins
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B7-H1 Antigen
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CD274 protein, human
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CD28 Antigens
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Interleukin-7 Receptor alpha Subunit
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PDCD1 protein, human
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Programmed Cell Death 1 Receptor
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Tumor Necrosis Factor Receptor Superfamily, Member 7