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 su bsets and natural killer (NK) cells in controlling murine cytomegalovi rus (MCMV) replication has been investigated, Genetically susceptible BALB/c and A/J, moderately resistant C57BL/10, and resistant CBA/CaH m ouse strains were treated with monoclonal antibodies (MAb) to the CD4 and CD8 markers and the extent of MCMV replication in major target tis sues was determined, Both mouse strain-specific and tissue-specific ef fects were observed, CBA/CaH and C57BL/10 mice were found not to requi re CD4(+) or CD8(+) T cells for control of MCMV replication in the spl een or liver, In contrast, in A/J mice, as well as BALB/c mice, the CD 8(+) T cell population was primarily responsible for the clearance of virus from these tissues, However, in all strains of mice, CD4(+) T ce lls were required for delayed type hypersensitivity and antibody respo nses, and for virus clearance in the salivary glands, The dependence o f mice with the BALE genetic background on CD8(+) T cells for limitati on of acute MCMV infection was found to be negated in the BALB.BG-Cmv1 (r) congenic strain, in which an effective NK cell response has been g enerated through the introduction of the resistant Cmv1(r) allele from C57BL/6 mice. Depletion of NK cells in the BALB.B6-Cmv1(r) strain usi ng anti-NK1.1 MAb restored the role of CD8(+) T cells in mediating vir al clearance, These analyses demonstrate that some, but not all, strai ns of mice use CD8(+) T cells to control MCMV replication and that eve n when CD8(+) T cell-dependence exists, this can be circumvented by an appropriate NK cell response.