Schmitt E, Germann T, Goedert S, Hoehn P, Huels C, Koelsch S, Kühn R, Müller W, Palm N, Rüde E
Institute for Immunology, University of Mainz, Germany.
J Immunol. 1994 Nov 1;153(9):3989-96.
Dense CD4+ T cells isolated from naive mice produce only trace amounts of IL-9 when stimulated by immobilized anti-CD3 in combination with anti-CD28 Abs. In this situation, IL-9 production is significantly stimulated by TGF-beta and further enhanced by the addition of IL-4, which, by itself, has only a minimal influence. IFN-gamma was found to inhibit the enhancing effect of IL-4. However, increasing amounts of IL-4 in the presence of a constant concentration of IFN-gamma could overcome the inhibitory activity of IFN-gamma. The application of CD4+ T cells isolated from IL-2 knockout mice unequivocally revealed that IL-2 is essential for the production of IL-9 by T cells. In addition, the use of T cells from IL-4 knockout mice elucidated that the basic (IL-2 + TGF-beta) mediated IL-9 production is independent of IL-4. Therefore, our results demonstrate that optimal IL-9 production of naive dense CD4+ T cells is positively regulated at different levels: 1) by IL-2, which is essential for IL-9 secretion; 2) followed by TGF-beta, which promotes a considerable increase in IL-9 production above the level induced by IL-2; and 3) finally, by IL-4, which requires the presence of IL-2 and TGF-beta to strongly enhance the production of IL-9. IFN-gamma inhibits the production of IL-9 mainly at the level of IL-4 by neutralizing the effect of this cytokine.
从未接触过抗原的小鼠中分离出的密集CD4+ T细胞，在固定化抗CD3与抗CD28抗体联合刺激时，仅产生微量的IL-9。在这种情况下，TGF-β可显著刺激IL-9的产生，而添加IL-4可进一步增强其产生，不过IL-4单独作用时影响极小。发现IFN-γ可抑制IL-4的增强作用。然而，在IFN-γ浓度恒定的情况下增加IL-4的量，可克服IFN-γ的抑制活性。应用从IL-2基因敲除小鼠中分离出的CD4+ T细胞明确显示，IL-2对于T细胞产生IL-9至关重要。此外，使用来自IL-4基因敲除小鼠的T细胞表明，基本的（IL-2 + TGF-β）介导的IL-9产生不依赖于IL-4。因此，我们的结果表明，未接触过抗原的密集CD4+ T细胞的最佳IL-9产生在不同水平受到正向调节：1）由IL-2调节，IL-2是IL-9分泌所必需的；2）其次是TGF-β，它可使IL-9产生量比IL-2诱导的水平大幅增加；3）最后是IL-4，它需要IL-2和TGF-β的存在才能强烈增强IL-9的产生。IFN-γ主要通过中和这种细胞因子的作用在IL-4水平抑制IL-9的产生。
