Regulation of the IL-12 receptor beta2 subunit by soluble antigen and IL-12 in vivo

Eur J Immunol. 1998 Jan;28(1):209-20. doi: 10.1002/(SICI)1521-4141(199801)28:01<209::AID-IMMU209>3.0.CO;2-S.

Abstract

Continuous administration of soluble protein antigen to BALB/c mice inhibits the development of Th1 and induces selective differentiation of Th2 cells. Here we show that interleukin (IL)-12, administered together with soluble protein through a mini-osmotic pump implanted subcutaneously, not only prevents the inhibition of Th1 cell development, but stimulates higher interferon (IFN)-gamma production than in mice receiving IL-12 alone. In parallel to co-stimulation of Th1 cell development, co-administration of IL-12 blocks the Th2 response induced by soluble protein. IL-12 administered in adjuvant with antigen or intraperitoneally 2 days after the immunization does not break the inhibition of Th1 but can still decrease the Th2 response induced by pretreatment with soluble protein antigen. In contrast to IL-12, co-administration of IL-2 or IFN-gamma does not affect the diversion to Th2 induced by soluble antigen. Thus IL-12, but not IL-2 nor IFN-gamma, converts in vivo the inhibitory signal for Th1 cell development delivered by soluble antigen into an immunogenic one, while blocking a positive signal for Th2 cell differentiation. A molecular basis for the co-stimulation of Th1 priming and the prevention of Th2 differentiation by IL-12 in vivo is provided by the observation that transcripts encoding the IL-12 receptor beta2 chain, which is required for IL-12 signaling and Th1 cell development, are selectively inhibited by soluble antigen but are enhanced by IL-12 co-administration.

MeSH terms

  • Animals
  • Antigens / immunology*
  • Cell Differentiation
  • Female
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / immunology
  • Immunization
  • Infusion Pumps, Implantable
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / pharmacology*
  • Interleukin-2 / pharmacology
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Mice
  • Mice, Inbred BALB C
  • Muramidase / immunology*
  • Ovalbumin / immunology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Interleukin / biosynthesis*
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-12
  • Solubility
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*

Substances

  • Antigens
  • Il12rb2 protein, mouse
  • Interleukin-2
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • Ovalbumin
  • Muramidase