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 t he ligation of CD40. In the present experiments, IL-12 is shown to be produced by murine spleen antigen-presenting cells (APC) by interactio n with T helper 1 (Th1) 1 clones through CD40-CD40 ligand (CD40L) inte raction, 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 inh ibit the IL-12 production induced by Th1 clones. In the presence of an ti-IL-10 monoclonal antibodies splenic APC interacting with Th2 clones produced IL-12. These results indicate that IL-10 produced by Th2 cel ls stimulated with antigen suppress IL-12 production of APC interactin g with Th2 cells. IL-12 is composed of two subunits, p35 and p40. In o ur experiments, p40 mRNA accumulation was shown to be affected by IL-1 0 more severely than the accumulation of p35 mRNA, indicating that IL- 10 regulates IL-12 production by APC mainly by affecting p40 mRNA accu mulation.