ROLE OF TRANSFORMING GROWTH-FACTOR-BETA IN THE PREFERENTIAL INDUCTIONOF T-HELPER CELLS OF TYPE-1 BY STAPHYLOCOCCAL ENTEROTOXIN-B

Stimulation of murine CD4+ T cells with staphylococcal enterotoxin B ( SEB) results in the preferential development of T helper (Th) 1 cells [i.e. high interferon (IFN)-gamma and low interleukin (IL)-4, IL-5 and IL-10]; whereas in response to plate-bound anti-CD3 or anti-T cell re ceptor-alphabeta, Th1 as well as Th2 cells develop. In the present stu dy, we examined the mechanism which is responsible for the selective T h1 development in the SEB system.The addition of IL-4 resulted in a st rong development of Th2 cells showing that SEB stimulation can result in Th2 differentiation. Co-stimulation with anti-CD28 was insufficient in this regard. Lack of Th2 development in the SEB system was in part due to the inhibitory effect of endogenously produced transforming gr owth factor-beta (TGF-beta), because anti-TGF-beta allowed the develop ment of Th2 cells. Similarly, TGF-beta inhibited Th2 development and s timulated Th1 development in the anti-CD3 system. This shift was only partially prevented by also including IL-4 in the cultures.The effects of TGF-beta could only partially be explained by stimulation of IFN-g amma or inhibition of IL-4 as intermediatory cytokines: (1) TGF-beta s timulated Th1 development even in the presence of anti-IL-4 and anti-I FN-gamma, and (2) a strong inhibitory effect of anti-TGF-beta on Th1 d evelopment was still observed when anti-IL-4 and IFN-gamma were simult aneously added to the cultures. It is concluded that SEB favors Th1 de velopment by stimulation of TGF-beta production. Inhibition of Th2 dev elopment by TGF-beta is due, in part, to inhibition of IL-4 and stimul ation of IFN-gamma, and, in part, to a direct effect of TGF-beta on th e responding T cells.