Negative feedback mechanism suppresses interleukin‐12 production by antigen‐presenting cells interacting with T helper 2 cells

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Abstract
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) 1 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.