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

Craig D. Peacock, Patricia Price

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalImmunology and Cell Biology
Volume77
Issue number2
DOIs
StatePublished - Apr 19 1999

Keywords

  • Cytomegalovirus
  • Interleukin-12
  • MAIDS
  • NK cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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