Abstract
CD8(+) T cells use a number of effector mechanisms to protect the host against infection. We have studied human CD8(+) T cells specific for CMV pp65(495-503) epitope, or for staphylococcal enterotoxin B, for the expression patterns of five cytokines and cytolytic effector molecules before and after antigenic stimulation. Ex vivo, the cytolytic molecule granzyme B was detected in a majority of circulating CMV-specific CD8(+) T cells, whereas perforin was rarely expressed. Both were highly expressed after Ag-specific activation accompanied by CD45RO up-regulation. TNF-alpha, IFN gamma, and IL-2 were sequentially acquired on recognition of Ag, but surprisingly, only around half of the CMV-specific CD8(+) T cells responded to antigenic stimuli with production of any cytokine measured. A dominant population coexpressed TNF-alpha and IFN-gamma, and cells expressing TNF-alpha only, IFN-gamma only, or all three cytokines together also occurred at lower but clearly detectable frequencies. Interestingly, perforin expression and production of IFN-gamma and TNF-alpha in CD8(+) T cells responding to staphylococcal enterotoxin B appeared to be largely segregated, and no IL-2 was detected in perforin-positive cells. Together, these data indicate that human CD8(+) T cells can be functionally segregated in vivo and have implications for the understanding of human CD8(+) T cell differentiation and specialization and regulation of effector mechanisms.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, Surface / biosynthesis
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Biomarkers
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / enzymology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / virology
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Cell Differentiation / immunology
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Cell Line
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Cytokines / biosynthesis
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Cytokines / physiology*
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Cytotoxicity, Immunologic / physiology*
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism
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Granzymes
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Humans
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Immunophenotyping
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Interferon-gamma / biosynthesis
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Interleukin-2 / biosynthesis
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / physiology
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Perforin
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Phosphoproteins / immunology
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Phosphoproteins / metabolism
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Pore Forming Cytotoxic Proteins
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Serine Endopeptidases / biosynthesis
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Serine Endopeptidases / physiology
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T-Lymphocyte Subsets / enzymology
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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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T-Lymphocytes, Cytotoxic / cytology
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T-Lymphocytes, Cytotoxic / enzymology
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / virology
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Tumor Necrosis Factor-alpha / biosynthesis
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Viral Matrix Proteins / immunology
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Viral Matrix Proteins / metabolism
Substances
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Antigens, Surface
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Biomarkers
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Cytokines
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Epitopes, T-Lymphocyte
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Interleukin-2
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Membrane Glycoproteins
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Phosphoproteins
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Pore Forming Cytotoxic Proteins
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Tumor Necrosis Factor-alpha
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Viral Matrix Proteins
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cytomegalovirus matrix protein 65kDa
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Perforin
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Interferon-gamma
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GZMB protein, human
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Granzymes
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Serine Endopeptidases