LOW-DOSE TGF-BETA ATTENUATES IL-12 RESPONSIVENESS IN MURINE TH CELLS

Expression of IL-12Rs is one important checkpoint for Th1 development. BALB/c D011.10 CD4(+) T cells stimulated by Ag in neutral conditions lose expression of the IL-12R beta 2 subunit and become unresponsive t o IL-12. In contrast, B10.D2 or F-1 (BALB/c x B10.D2) D011.10 CD4(+) T cells maintain IL-12R beta 2 expression when stimulated similarly. He re we show that the loss of IL-12 responsiveness by BALB/c T cells inv olves the action of endogenous TGP-beta, BALB/c T cells stimulated in the presence of anti-TGF-beta specifically maintain IL-12 responsivene ss, express IL-12R beta 2 mRNA, and can stimulate nitric oxide product ion in peritoneal exudate cells. Low concentrations of TGF-beta added exogenously during primary activation of B10.D2 or F-1 T cells signifi cantly inhibit their development of IL-12 responsiveness. These effect s of anti-TGF-beta are dependent on endogenous IFN-gamma and are inhib ited by exogenously added IL-4, Thus, at least one effect of TGF-beta on Th1/Th2 development may be the attenuation of IL-12R beta 2 express ion.