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

被引:77
作者
NAGELKERKEN, L
GOLLOB, KJ
TIELEMANS, M
COFFMAN, RL
机构
[1] TNO, INST AGING & VASC RES, 2313 AD LEIDEN, NETHERLANDS
[2] DNAX RES INST MOLEC & CELLULAR BIOL INC, MOLEC & CELLULAR BIOL RES INST, PALO ALTO, CA USA
关键词
STAPHYLOCOCCAL ENTEROTOXIN-B; TRANSFORMING GROWTH FACTOR-BETA; CD4; INTERFERON-GAMMA; INTERLEUKIN-4;
D O I
10.1002/eji.1830230938
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-alphabeta, 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.
引用
收藏
页码:2306 / 2310
页数:5
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