T cells expressing the Vgamma1 T-cell receptor enhance virus-neutralizing antibody response during coxsackievirus B3 infection of BALB/c mice: differences in male and female mice

Viral Immunol. 2005;18(4):730-9. doi: 10.1089/vim.2005.18.730.


Coxsackievirus B3 infection causes severe cardiac inflammation in male but not female mice. CD3+ T cells and T cells expressing the Vgamma4 T cell receptor (TCR) predominate in the cardiac inflammatory cell infiltrate in infected male BALB/c mice. Infected females have mostly CD19+ (B lymphocyte) and Vgamma1+ cells. No significant differences in CD11b+ (monocyte) cells were observed between the sexes. Infected males showed a predominant CD4+Th1 (IFNgamma+) response, whereas females showed a predominant CD4+Th2 response. The importance of IFNgamma for myocarditis susceptibility and IL-4 for protection was confirmed using IFN-gamma-/- and IL-4-/- mice. Antibody depletion of Vgamma1+ cells augmented myocarditis susceptibility, whereas antibody depletion of Vgamma4+ cells was protective. Cardiac virus titers inversely correlated with virus neutralizing antibodies and showed that Vgamma1+ cells are important for virus neutralizing antibody response. IFNgamma affected the Vgamma4+ cell response in the heart, as IFNgamma-/- mice had few Vgamma4+ cells; but exogenous administration of recombinant IFNgamma to IFNgamma-/- mice restored myocarditis susceptibility, Th1 bias, and Vgamma4+ cell infiltration of the myocardium. These results demonstrate that two gammadelta+ T cell populations, Vgamma1+ and Vgamma4+, have different functions during myocarditis, in that Vgamma1+ cells promote humoral immunity and protection whereas Vgamma4+ cells are pathogenic.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Coxsackievirus Infections / immunology*
  • Coxsackievirus Infections / pathology
  • Coxsackievirus Infections / virology
  • Enterovirus B, Human / immunology*
  • Female
  • Heart / virology
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Myocarditis / pathology
  • Myocarditis / virology
  • Myocardium / immunology
  • Myocardium / pathology
  • Neutralization Tests
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Recombinant Proteins
  • Sex Characteristics
  • T-Lymphocyte Subsets / immunology*


  • Antibodies, Viral
  • Receptors, Antigen, T-Cell, gamma-delta
  • Recombinant Proteins
  • Interleukin-4
  • Interferon-gamma