LYMPHOCYTES PROTECT AGAINST AND ARE NOT REQUIRED FOR REOVIRUS-INDUCEDMYOCARDITIS

Many studies suggest that host lymphocytes are damaging, rather than p rotective, in virally induced myocarditis. We have investigated the ro le of lymphocyte-based immunity in murine myocarditis by using a myoca rditic reovirus (reovirus serotype 3 8B), nonmyocarditic reoviruses, a doptive transfer experiments, and mice with severe combined immunodefi ciency (SCID mice). Prior to infection, passive transfer of monoclonal antibodies specific for 8B capsid proteins protected neonatal mice ag ainst 8B-induced myocarditis, indicating that humoral immunity can pro tect against myocarditis. Some monoclonal antibodies acted by blocking viral spread to and/or replication in the heart. Passive transfer of reovirus-immune, but not naive, spleen cells prior to infection protec ted neonatal mice from 8B-induced myocarditis. Depletion of either CD4 or CD8 T cells resulted in increased viral titer in the heart but did not abrogate immune cell-mediated protection against myocardial injur y. This shows that both CD4 and CD8 T cells can act independently to p rotect myocardial tissue from reovirus infection. In addition, reoviru s 8B caused extensive myocarditis in SCID mice. This confirms a prior report (B. Sherry, F. J. Schoen, E. Wenske, and B. N. Fields, J. Virol . 63:4840-4849, 1989) that T cells are not required for reovirus-induc ed myocarditis and demonstrates for the first time that B cells are no t required for reovirus-induced myocarditis. We used SCID mice and a p anel of reoviruses to assess (i) the relationship between growth in th e heart and myocardial damage and (ii) the possibility that nonmyocard itic reoviruses exhibit a myocarditic phenotype in the absence of func tional lymphocytes. Growth in the heart was not the sole determinant o f myocarditic potential in SCID mice. Although 8B induced myocarditis in SCID mice, no or minimal myocarditis was found in SCID mice infecte d with four reovirus strains previously shown (B. Sherry and B. N. Fie lds J. Virol. 63:4850-4856, 1989) to be nonmyocarditic or poorly myoca rditic in normal neonatal mice. We conclude that (i) humoral immunity and cellular immunity are protective against, and not required for, re ovirus-induced myocarditis and (ii) the potential to induce cardiac da mage is a property of the virus independent of lymphocyte-based immuni ty.