Negative feedback mechanism suppresses interleukin-12 production by antigen-presenting cells interacting with T helper 2 cells.
Interleukin-12 (IL-12) has been shown to be produced by monocytes by the ligation of CD40. In the present experiments, IL-12 is shown to be produced by murine spleen antigen-presenting cells (APC) by interaction with T helper 1 (Th1) clones through CD40-CD40 ligand (CD40L) interaction, but not with Th2 clones. The IL-12 production induced by the Th1 clone interaction was inhibited by the addition of exogenous IL-10. Th2 clones were shown to produce a sufficient amount of IL-10 to inhibit the IL-12 production induced by Th1 clones. In the presence of anti-IL-10 monoclonal antibodies splenic APC interacting with Th2 clones produced IL-12. These results indicate that IL-10 produced by Th2 cells stimulated with antigen suppress IL-12 production of APC interacting with Th2 cells. IL-12 is composed of two subunits, p35 and p40. In our experiments, p40 mRNA accumulation was shown to be affected by IL-10 more severely than the accumulation of p35 mRNA, indicating that IL-10 regulates IL-12 production by APC mainly by affecting p40 mRNA accumulation.
Hino
A
A
Department of Allergology, Institute of Medical Science, University of Tokyo, Japan.
Nariuchi
H
H
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D001483:Base Sequence; D002450:Cell Communication / Q000276:immunology*; D002999:Clone Cells; D015536:Down-Regulation / Q000276:immunology*; D005246:Feedback; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D016753:Interleukin-10; D018664:Interleukin-12