The role of IL-12 in the control of MCMV is fundamentally different in mice with a retroviral immunodeficiency syndrome (MAIDS).
The present study investigates the susceptibility of C57BL mice exhibiting T cell immunodeficiency and lymphadenopathy induced by LP-BM5 murine leukaemia virus (MAIDS) to murine cytomegalovirus (MCMV). Treatment of normal (M-) mice with anti-IL-12 increased the contribution of IgG1 to the hypergammaglobulinaemia induced by MCMV, consistent with a shift towards a Th2 phenotype. This impaired control of early MCMV replication in the liver, with little effect in the spleen. Control of hepatic infection correlated with a vigorous splenic NK cytotoxic response in a subgroup of IL-12-depleted M- mice that remained healthy, while others became moribund. Mortality in IL-12-depleted MAIDS (M+) mice given MCMV was ultimately greater than in M- controls, but was delayed despite high levels of MCMV in the liver. IL-12 was required for optimal control of MCMV replication in M+ mice. This may involve cytotoxic activity because similar levels of infection were seen in bg/bg M+ mice, where the beige mutation impairs the formation of cytotoxic granules. Hence the ability of M+ mice to tolerate high titres of MCMV during acute infection may enable innate cytotoxic responses to clear MCMV. Interleukin-12 depletion of M- mice also increased salivary gland MCMV titres and depressed delayed-type hypersensitivity responses to MCMV antigen, normally mediated by CD4+ T cells. These changes were not observed in IL-12-depleted M+ mice.
Peacock
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Department of Microbiology, University of Western Australia, Nedlands.
Price
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D006524:Hepatitis, Viral, Animal / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology*; D009052:Leukemia Virus, Murine / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology*; D018146:Muromegalovirus / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014779:Virus Replication
D018664:Interleukin-12