The role of IL-12 in the control of MCMV is fundamentally different in mice with a retroviral immunodeficiency syndrome (MAIDS)

• Published in: Immunology and cell biology Vol. 77; no. 2; p. 131
• Main Authors: Peacock, C D, Price, P
• Format: Journal Article
• Language: English
• Published: United States 01.04.1999
• Subjects: Animals; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cytotoxicity, Immunologic - immunology; Disease Susceptibility - immunology; Female; Hepatitis, Viral, Animal - immunology; Herpesviridae Infections - immunology; Interleukin-12 - immunology; Leukemia Virus, Murine - immunology; Leukemia Virus, Murine - physiology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Murine Acquired Immunodeficiency Syndrome - immunology; Muromegalovirus - immunology; Spleen - immunology; Virus Replication
• ISSN: 0818-9641
• DOI: 10.1046/j.1440-1711.1999.00810.x

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.