Evidence of positive cross-regulation on Th1 by Th2 and antigen-presentingcells: Effects on Th1 induced by IL-4 and IL-12

The response of Th cells to cytokines is normally strictly regulated, such that following antigenic stimulation, Th cells respond for only a short per iod of time, after which they become refractory to cytokine-mediated effect s. IL-12, a costimulator of Th1 having no proliferation-inducing capacity o f its own, allows Th1 clones and lines to respond to IL-4, when they would otherwise be unable to respond to this cytokine, Cells that have proliferat ed in response to IL-4 plus IL-12 are fully able to be subsequently activat ed by specific Ag and APC, Additionally, the response to IL-4 of Th1 effect or cells derived from normal murine spleen is enhanced significantly by IL- 12, Furthermore, in the presence of IL-12, stimulated Th2 can induce prolif eration of Th1 via IL-4 production, in a dual chamber culture system. We hy pothesize that the effects of IL-4 and IL-12 represent a novel, positive cr oss-regulatory pathway that acts on Th1, and is mediated by Th2 (the IL-4 s ource) and APC (the IL-12 source). We propose this as a way for a Th2 immun e response to positively influence an ongoing or waning Th1 response.