Abstract
Coxsackievirus B3 (CVB3) induces myocarditis, an inflammation of the myocardium, in C57Bl/6 male mice but not in mice lacking γδ+ T cells [γδ knockout (γδKO)]. Suppression of myocarditis in γδKO mice corresponds to an increase in CD4(+) CD25(+) FoxP3(+) T regulatory cells. A subpopulation of the T regulatory cells in infected γδKO mice expressed high levels of CD1d, a non-classical major histocompatibility complex class 1-like molecule. Adoptive transfer of CD1d(+) and CD1d(-) CD4(+) CD25(+) cells into infected C57Bl/6 recipients showed that the CD1d(+) subpopulation is substantially more suppressive than the CD1d(-) subpopulation. T cells expressing the γδ T-cell receptor comprised approximately 30-50% of the infiltrating lymphoid cells in the hearts of myocarditic C57Bl/6 mice and approximately half of the γδ+ cells expressed the Vγ4 T-cell receptor. The Vγ4+ cells lysed T regulatory cells from γδKO mice but not from wild-type (C57Bl/6) animals. Lysis was inhibited by antibody to CD1d and zVAD-fmk, a pan-caspase inhibitor. The Vγ4-γδ+ cells were not lytic to T regulatory cells and did not promote myocarditis. These results demonstrate that Vγ4+ cells selectively abrogate T regulatory cells through recognition of CD1d expressed on the regulatory cells and caspase-dependent apoptosis.
© 2010 The Author. Immunology © 2010 Blackwell Publishing Ltd.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adoptive Transfer
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Amino Acid Chloromethyl Ketones / pharmacology
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD1d / immunology
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Antigens, CD1d / metabolism*
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Apoptosis / drug effects
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Apoptosis / immunology
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Cell Count
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Coxsackievirus Infections / complications
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Coxsackievirus Infections / immunology
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Coxsackievirus Infections / pathology
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Coxsackievirus Infections / virology
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Cysteine Proteinase Inhibitors / pharmacology
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Forkhead Transcription Factors / metabolism
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Male
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Mice
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Mice, 129 Strain
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Mice, Inbred C57BL
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Mice, Knockout
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Myocarditis / etiology
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Myocarditis / immunology
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Myocarditis / pathology
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Myocarditis / virology
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Receptors, Antigen, T-Cell, gamma-delta / metabolism*
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Spleen / cytology
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Spleen / immunology
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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-Lymphocytes, Regulatory / cytology*
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
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T-Lymphocytes, Regulatory / pathology
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Th1 Cells / cytology
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Th1 Cells / immunology
Substances
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Amino Acid Chloromethyl Ketones
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Antibodies, Monoclonal
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Antigens, CD1d
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Cd1d1 protein, mouse
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Cysteine Proteinase Inhibitors
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Receptors, Antigen, T-Cell, gamma-delta
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone