Resistance to Murine Cytomegalovirus By CASSANDRA M. LAWSON, * t PH IL IP D. HODGKIN ~ AND


The ability of mice to survive infection with murine cytomegalovirus (MCMV) is known to be influenced by genes of the major histocompatibility complex (MHC). One hypothesis to account for this association is that MHC-linked resistance to MCMV is an 'immune response ' gene effect, caused by differences in the strength of the MHC-restricted T cell response of mouse strains with different MHC haplotypes. Therefore, removal of T cell responses in mouse strains differing only at the MHC should render them equally susceptible to the virus infection. To test this hypothesis, the immunosuppressive drug cyclosporin (CsA) was used to reduce T cell responses in inbred congenic mouse strains carrying either a resistant or susceptible MHC haplotype. CsA reduced the delayed-type hypersensitivity (DTH) response to MCMV in both resistant and susceptible mouse strains to background levels, equivalent to control uninfected mice. CsA treatment had little effect on the susceptibility of C57BL/I 0 and B 10. B R mice to the virus and the differences in susceptibility between these strains remained. In contrast, CsA increased the susceptibility of the genetically susceptible BALB/c mice (H-2 d) by 100-fold and increased the susceptibility o

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