γδ T lymphocytes kill T regulatory cells through CD1d.
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.
Department of Pathology, University of Vermont, Colchester, VT 05446, USA. Sally.Huber@uvm.edu
Sally A
SA
Huber
D019264:Adoptive Transfer; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002452:Cell Count; D003384:Coxsackievirus Infections / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000821:virology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000821:virology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology
D000590:Amino Acid Chloromethyl Ketones; D000911:Antibodies, Monoclonal; D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; D015853:Cysteine Proteinase Inhibitors; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone