ABSTRACT
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-γ+]) response to the virus, and a predominance of γδ 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 γδ 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 γδ 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 γδ Τ cells on lymphocyte subpopulations may regulate the cytokine response to CVB3 infection and pathogenicity.
High Expression of Fas Ligand by Synovial Fluid-Derived γδ T Cells in Lyme Arthritis
