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

Abstract

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.

• Authors: C D Peacock, P Price
• Journal: Immunology and cell biology (Immunol Cell Biol) Vol. 77 Issue 2 Pg. 131-8 (Apr 1999) ISSN: 0818-9641 [Print] United States
• PMID: 10234548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-12

Topics

• 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, physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Murine Acquired Immunodeficiency Syndrome (immunology)
• Muromegalovirus (immunology)
• Spleen (immunology)
• Virus Replication