Gammadelta T cells promote a Th1 response during coxsackievirus B3 infection in vivo: role of Fas and Fas ligand

J Virol. 2002 Jul;76(13):6487-94. doi: 10.1128/jvi.76.13.6487-6494.2002.


Fas/Fas ligand (FasL) interactions regulate disease outcome in coxsackievirus B3 (CVB3)-induced myocarditis. MRL(+/+) mice infected with CVB3 develop severe myocarditis, a dominant CD4(+) Th1 (gamma interferon [IFN-gamma(+)]) response to the virus, and a predominance of gammadelta T cells in the myocardial infiltrates. MRL lpr/lpr and MRL gld/gld mice, which lack normal expression of Fas and express a mutated FasL, respectively, have minimal myocarditis and show a dominant CD4(+) Th2 (interleukin-4 [IL-4(+)]) phenotype to CVB3. Spleen cells from virus-infected wild-type, lpr, and gld animals proliferate equally to virus in vitro. Adoptive transfer of gammadelta T cells from hearts of CVB3-infected MRL(+/+) mice (FasL(+)) into infected MRL gld/gld recipients (FasL(-)/Fas(+)) restores both disease susceptibility and Th1 cell phenotype. However, transfer of these cells into MRL lpr/lpr recipients (FasL(+)/Fas(-)) did not promote myocarditis and the viral response remained Th2 biased. This paralleled the expression of very high surface levels of FasL by myocardial gammadelta T cells, as well as their propensity to selectively lyse Th2 virus-specific CD4(+) T cells. These results demonstrate that Fas/FasL interactions conferred by gammadelta T cells on lymphocyte subpopulations may regulate the cytokine response to CVB3 infection and pathogenicity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Enterovirus B, Human / immunology
  • Enterovirus B, Human / pathogenicity*
  • Enterovirus Infections / immunology
  • Enterovirus Infections / physiopathology
  • Enterovirus Infections / virology
  • Fas Ligand Protein
  • Interferon-gamma / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred MRL lpr
  • Myocarditis / immunology
  • Myocarditis / physiopathology*
  • Myocarditis / virology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Th1 Cells / immunology*
  • fas Receptor / genetics
  • fas Receptor / physiology*


  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • fas Receptor
  • Interferon-gamma