Delayed-type hypersensitivity responses to murine cytomegalovirus in genetically resistant and susceptible strains of mice

Abstract

The delayed-type hypersensitivity (DTH) response in mice infected with murine cytomegalovirus (MCMV) was measured by ear swelling following a challenge with heat-treated MCMV. DTH was dose-dependent and could be detected as early as 3 days post-infection with peak responses occurring between days 15 and 21 post-infection. The DTH response was found to be specific for MCMV since it could not be elicited by either herpes simplex virus type 1 or influenza A virus in MCMV-primed mice. The elicited DTH response was greater in mice primed with attenuated compared with virulent MCMV. The DTH response was shown to correlate positively with the genetically determined resistance status of mouse strains to this virus. Previous research has shown that resistance to lethal infection with MCMV is controlled by H-2-linked genes since mice having the k haplotype are more resistant than mice having the b or d haplotype of the H-2-complex. Also, non-H-2-linked genes in CBA, C3H, C57BL/10 and probably other strains confer resistance. Resistant strains (C3H [H-2k], CBA [H-2k]) developed greater DTH responses than those of susceptible strains (BALB/c [H-2d], C57BL/10 [H-2b]) inoculated with the same dose of virus. In addition, the genetically resistant mouse strains B10.BR [H-2k] and BALB.K [H-2k] gave a significantly greater DTH response than that of the corresponding congenic strains C57BL/10 [H-2b], BALB/c [H-2d] and BALB.B [H-2b] which are genetically susceptible to the virus. Also, the DTH response of C57BL/10 [H-2b] was significantly higher than that of BALB.B [H-2b] which correlates with their relative genetic resistance to MCMV, indicating the importance of non-H-2-linked genes. Furthermore, in addition to the response of greater magnitude, resistant strains (CBA, C3H, B10.BR) produced DTH responses to MCMV by day 3 compared with day 5 post-infection for susceptible BALB/c mice. These findings indicate that the magnitude and the time of appearance of the DTH response correlates positively with the genetically determined resistance status, although the role of DTH responses in controlling MCMV infections remains to be determined.