Role of transforming growth factor-βthe 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)‐γ and low interleukin (IL)‐4, IL‐5 and IL‐10]; whereas in response to plate‐bound anti‐CD3 or anti‐T cell receptor‐αβ, 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 inTh2 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‐β (TGF‐β), because anti‐TGF‐β allowed the development of Th2 cells. Similarly, TGF‐β 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‐β could only partially be explained by stimulation of IFN‐γ or inhibition of IL‐4 as intermediatory cytokines: (1) TGF‐β stimulated Th1 development even in the presence of anti‐IL‐4 and anti‐IFN‐γ, and (2) a strong inhibitory effect of anti‐TGF‐β on Th1 development was still observed when anti‐IL‐4 and IFN‐γ were simultaneously added to the cultures. It is concluded that SEB favors Th1 development by stimulation of TGF‐β production. Inhibition of Th2 development by TGF‐β is due, in part, to inhibition of IL‐4 and stimulation of IFN‐γ, and, in part, to a direct effect of TGF‐β on the responding T cells.