REGULATION OF THE IL-12 RECEPTOR BETA-2 SUBUNIT BY SOLUBLE-ANTIGEN AND IL-12 IN-VIVO

Continuous administration of soluble protein antigen to BALB/c mice in hibits the development of Th1 and induces selective differentiation of Th2 cells. Here we show that interleukin (IL)-12, administered togeth er with soluble protein through a mini-osmotic pump implanted subcutan eously, not only prevents the inhibition of Th1 cell development, but stimulates higher interferon (IFN)-gamma production than in mice recei ving IL-12 alone. In parallel to costimulation of Th1 cell development , co-administration of IL-12 blocks the Th2 response induced by solubl e protein. IL-12 administered in adjuvant with antigen or intraperiton eally 2 days after the immunization does not break the inhibition of T h1 but can still decrease the Th2 response induced by pretreatment wit h soluble protein antigen. In contrast to IL-12, coadministration of I L-2 or IFN-gamma does not affect the diversion to Th2 induced by solub le antigen. Thus IL-12, but not IL-2 nor IFN-gamma, converts in vivo t he inhibitory signal for Th1 cell development delivered by soluble ant igen 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 recep tor beta 2 chain, which is required for IL-12 signaling and Th1 cell d evelopment, are selectively inhibited by soluble antigen but are enhan ced by IL-12 co-administration.