Gorham J D, Güler M L, Fenoglio D, Gubler U, Murphy K M
Dartmouth Medical School-DHMC, Department of Pathology, Lebanon, NH 03756, USA.
J Immunol. 1998 Aug 15;161(4):1664-70.
Expression of IL-12Rs is one important checkpoint for Th1 development. BALB/c DO11.10 CD4+ T cells stimulated by Ag in neutral conditions lose expression of the IL-12R beta 2 subunit and become unresponsive to IL-12. In contrast, B10.D2 or F1 (BALB/c x B10.D2) DO11.10 CD4+ T cells maintain IL-12R beta 2 expression when stimulated similarly. Here we show that the loss of IL-12 responsiveness by BALB/c T cells involves the action of endogenous TGF-beta. BALB/c T cells stimulated in the presence of anti-TGF-beta specifically maintain IL-12 responsiveness, express IL-12R beta 2 mRNA, and can stimulate nitric oxide production in peritoneal exudate cells. Low concentrations of TGF-beta added exogenously during primary activation of B10.D2 or F1 T cells significantly inhibit their development of IL-12 responsiveness. These effects of anti-TGF-beta are dependent on endogenous IFN-gamma and are inhibited 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 expression.
IL-12受体的表达是Th1细胞发育的一个重要检查点。在中性条件下由抗原刺激的BALB/c DO11.10 CD4+ T细胞会失去IL-12Rβ2亚基的表达，并且对IL-12无反应。相比之下，B10.D2或F1（BALB/c×B10.D2）DO11.10 CD4+ T细胞在受到类似刺激时会维持IL-12Rβ2的表达。在此我们表明，BALB/c T细胞对IL-12反应性的丧失涉及内源性TGF-β的作用。在抗TGF-β存在的情况下刺激的BALB/c T细胞特异性地维持对IL-12的反应性，表达IL-12Rβ2 mRNA，并能刺激腹腔渗出细胞产生一氧化氮。在B10.D2或F1 T细胞初次激活期间外源性添加低浓度的TGF-β会显著抑制它们对IL-12反应性的发育。抗TGF-β的这些作用依赖于内源性IFN-γ，并受到外源性添加的IL-4的抑制。因此，TGF-β对Th1/Th2发育的至少一种作用可能是减弱IL-12Rβ2的表达。
