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Journal of Virology, July 2002, p. 6487-6494, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6487-6494.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

T Cells Promote a Th1 Response during Coxsackievirus B3 Infection In Vivo: Role of Fas and Fas Ligand

Department of Pathology,¹ Immunobiology Program, The University of Vermont College of Medicine, Burlington, Vermont 05405²

Received 6 December 2001/ Accepted 3 April 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-⁺]) response to the virus, and a predominance of 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 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 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 T cells on lymphocyte subpopulations may regulate the cytokine response to CVB3 infection and pathogenicity.

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