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.
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.
Huber
Sally
S
Department of Pathology, University of Vermont, Colchester, Vermont 05446, USA. Sally.Huber@uvm.edu
Sartini
Danielle
D
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D029822:Enterovirus B, Human / Q000276:immunology*; D005260:Female; D006321:Heart / Q000821:virology; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009205:Myocarditis / Q000473:pathology / Q000821:virology; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D009500:Neutralization Tests; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D011994:Recombinant Proteins; D012727:Sex Characteristics; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000914:Antibodies, Viral; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma