γδ T lymphocytes kill T regulatory cells through CD1d

Immunology. 2010 Oct;131(2):202-9. doi: 10.1111/j.1365-2567.2010.03292.x. Epub 2010 Aug 16.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD1d / immunology
  • Antigens, CD1d / metabolism*
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Cell Count
  • Coxsackievirus Infections / complications
  • Coxsackievirus Infections / immunology
  • Coxsackievirus Infections / pathology
  • Coxsackievirus Infections / virology
  • Cysteine Proteinase Inhibitors / pharmacology
  • Forkhead Transcription Factors / metabolism
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocarditis / etiology
  • Myocarditis / immunology
  • Myocarditis / pathology
  • Myocarditis / virology
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology
  • Th1 Cells / cytology
  • Th1 Cells / immunology

Substances

  • Amino Acid Chloromethyl Ketones
  • Antibodies, Monoclonal
  • Antigens, CD1d
  • Cd1d1 protein, mouse
  • Cysteine Proteinase Inhibitors
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Receptors, Antigen, T-Cell, gamma-delta
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone