Effect of host genotype in determining the relative roles of natural killer cells and T cells in mediating protection against murine cytomegalovirus infection

The influence of host genotype on the relative importance of T cell subsets and natural killer (NK) cells in controlling murine cytomegalovirus (MCMV) replication has been investigated. Genetically susceptible BALB/c and A/J, moderately resistant C57BL/10, and resistant CBA/CaH mouse strains were treated with monoclonal antibodies (MAb) to the CD4 and CD8 markers and the extent of MCMV replication in major target tissues was determined. Both mouse strain-specific and tissue-specific effects were observed. CBA/CaH and C57BL/10 mice were found not to require CD4+ or CD8+ T cells for control of MCMV replication in the spleen or liver. In contrast, in A/J mice, as well as BALB/c mice, the CD8+ T cell population was primarily responsible for the clearance of virus from these tissues. However, in all strains of mice, CD4+ T cells were required for delayed type hypersensitivity and antibody responses, and for virus clearance in the salivary glands. The dependence of mice with the BALB genetic background on CD8+ T cells for limitation of acute MCMV infection was found to be negated in the BALB.B6-Cmv1(r) congenic strain, in which an effective NK cell response has been generated through the introduction of the resistant Cmv1(r) allele from C57BL/6 mice. Depletion of NK cells in the BALB.B6-Cmv1(r) strain using anti-NK1.1 MAb restored the role of CD8+ T cells in mediating viral clearance. These analyses demonstrate that some, but not all, strains of mice use CD8+ T cells to control MCMV replication and that even when CD8+ T cell-dependence exists, this can be circumvented by an appropriate NK cell response.