Abstract
Two prototypic types of virus-specific CD8(+) T cells can be found in latently infected individuals: CD45R0(+)CD27(+)CCR7(-) effector-memory, and CD45RA(+)CD27(-)CCR7(-) effector-type cells. It has recently been implied that CD45RA(+)CD27(-)CCR7(-) T cells are terminally differentiated effector cells and as such have lost all proliferative capacity. We show in this study, however, that stimulation of CMV-specific CD45RA(+)CD27(-)CCR7(-) T cells with their cognate peptide in concert with either CD4(+) help or IL-2, IL-15, or IL-21 in fact induces massive clonal expansion. Concurrently, these stimulated effector T cells change cell surface phenotype from CD45RA to CD45R0 and regain CCR7, while effector functions are maintained. Our data imply that CD45RA(+)CD27(-)CCR7(-) effector-type T cells contribute to immunity not only by direct execution of effector functions, but also by yielding progeny in situations of viral reinfection or reactivation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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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CD8-Positive T-Lymphocytes / virology*
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Cell Differentiation / immunology
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Cell Division / immunology
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Cells, Cultured
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Cytomegalovirus / immunology*
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Cytotoxicity Tests, Immunologic
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Epitopes, T-Lymphocyte / physiology*
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Humans
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Immunodominant Epitopes / physiology
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Immunophenotyping
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Interleukin-15 / physiology
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Interleukin-2 / physiology
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Interleukins / physiology
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Lymphocyte Activation*
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Phosphoproteins / physiology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / virology*
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Tuberculin / physiology
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Viral Matrix Proteins / physiology
Substances
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Epitopes, T-Lymphocyte
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Immunodominant Epitopes
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Interleukin-15
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Interleukin-2
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Interleukins
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Phosphoproteins
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Tuberculin
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Viral Matrix Proteins
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cytomegalovirus matrix protein 65kDa
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interleukin-21