Role of transforming growth factor-beta in the preferential induction of T helper cells of type 1 by staphylococcal enterotoxin B.

ABSTRACT

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 receptor-alpha beta, Th1 as well as Th2 cells develop. In the present study, we examined the mechanism which is responsible for the selective Th1 development in the SEB system. The addition of IL-4 resulted in a strong 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 growth factor-beta (TGF-beta), because anti-TGF-beta allowed the development of Th2 cells. Similarly, TGF-beta inhibited Th2 development and stimulated 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-gamma or inhibition of IL-4 as intermediatory cytokines (1) TGF-beta stimulated Th1 development even in the presence of anti-IL-4 and anti-IFN-gamma, and (2) a strong inhibitory effect of anti-TGF-beta on Th1 development was still observed when anti-IL-4 and IFN-gamma were simultaneously added to the cultures. It is concluded that SEB favors Th1 development by stimulation of TGF-beta production. Inhibition of Th2 development by TGF-beta is due, in part, to inhibition of IL-4 and stimulation of IFN-gamma, and, in part, to a direct effect of TGF-beta on the responding T cells.