Interleukin-12 can directly induce T-helper 1 responses in interferon-gamma (IFN-gamma) receptor-deficient mice, but requires IFN-gamma signalling to downregulate T-helper 2 responses

Immunology. 1999 Aug;97(4):588-94. doi: 10.1046/j.1365-2567.1999.00832.x.

Abstract

An in vivo model of pulmonary granuloma formation around embolized schistosome eggs was investigated as an environment in which to analyse a role for interleukin-12 (IL-12) in the differentiation of T-helper 1 (Th1) and Th2 subsets. Specifically, mice deficient for the interferon-gamma receptor (IFN-gammaR-/-) were used to determine the role for IL-12 in the absence of IFN-gamma-mediated signalling. We show that recombinant IL-12 administered to IFN-gammaR-/- mice caused the up-regulation of mRNA for IFN-gamma in lung tissue, and the secretion of abundant IFN-gamma by in vitro-cultured lymph node cells in response to egg antigens. This indicates that IL-12 can act independently of IFN-gamma to induce the development of Th1 cells. Administration of rIL-12 to wild-type mice markedly reduced the secretion of Th2-associated cytokines, IL-4 and IL-5. However, these cytokines were not dramatically reduced in IFN-gammaR-/- mice treated with IL-12. We conclude that inhibition of these cytokines by IL-12 is primarily dependent upon effective IFN-gamma signalling, although abrogation of T-cell derived IL-10 appeared to be dependent upon IL-12. We also show that increases in mRNA for the beta2 subunit of the IL-12 receptor and the p40 subunit of IL-12 after rIL-12 treatment were lower in IFN-gammaR-/- mice, compared to wild-type mice, indicating that their expression was primarily dependent upon IFN-gamma with only a minor role for IL-12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Down-Regulation / immunology
  • Granuloma / immunology
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology*
  • Interleukin-12 / immunology*
  • Interleukin-4 / biosynthesis
  • Interleukin-5 / biosynthesis
  • Mice
  • Mice, Inbred Strains
  • RNA, Messenger / genetics
  • Receptors, Interferon / deficiency
  • Receptors, Interferon / genetics
  • Recombinant Proteins / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schistosomiasis mansoni / immunology*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*

Substances

  • Interleukin-5
  • RNA, Messenger
  • Receptors, Interferon
  • Recombinant Proteins
  • interferon gamma receptor
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma