Lingnau K, Hoehn P, Kerdine S, Koelsch S, Neudoerfl C, Palm N, Ruede E, Schmitt E
Institute for Immunology, Johannes Gutenberg University, Mainz, Germany.
J Immunol. 1998 Nov 1;161(9):4709-18.
IL-4 was found to be the essential differentiation factor for Th2 cells and simultaneously to be a potent inhibitor of Th1 development that is induced by IFN-gamma and IL-12. Furthermore, it was demonstrated that TGF-beta can also inhibit Thl development. In this work, we demonstrate that polyclonal activation of Mel-14highCD4+ T cells by immobilized anti-alphabetaTCR mAb together with a mixture of IL-4 and TGF-beta can lead to the development of both Th1 and Th2 cells, depending on the concentration of these cytokines. Additional experiments revealed that Th1 induction by a combination of IL-4 and TGF-beta depends on the presence of endogenous IFN-gamma, and that this alternative Th1 development is further enhanced by IL-12, but is not dependent on this cytokine. Moreover, naive OVA323-339-specific Th cells that were stimulated by APCs and OVA323-339 peptide differentiated toward Th1 cells after priming in the presence of IL-4 in combination with TGF-beta. Hence, this finding confirmed the results obtained by polyclonal activation of naive CD4+ Th cells and implicates that this alternative Th1 development may also occur in vivo under the influence of TGF-beta and IL-4 independently of the Th1-promoting effect of IL-12.
白细胞介素-4被发现是Th2细胞的关键分化因子，同时也是由干扰素-γ和白细胞介素-12诱导的Th1细胞发育的强效抑制剂。此外，已证明转化生长因子-β也能抑制Th1细胞发育。在本研究中，我们证明，固定化抗αβTCR单克隆抗体与白细胞介素-4和转化生长因子-β的混合物共同对Mel-14highCD4+ T细胞进行多克隆激活，可导致Th1和Th2细胞的发育，这取决于这些细胞因子的浓度。进一步的实验表明，白细胞介素-4和转化生长因子-β联合诱导Th1细胞依赖于内源性干扰素-γ的存在，并且这种替代性Th1细胞发育会被白细胞介素-12进一步增强，但不依赖于这种细胞因子。此外，在存在白细胞介素-4和转化生长因子-β的情况下，经抗原呈递细胞和OVA323-339肽刺激的初始OVA323-339特异性Th细胞在启动后分化为Th1细胞。因此，这一发现证实了对初始CD4+ Th细胞进行多克隆激活所获得的结果，并表明这种替代性Th1细胞发育也可能在体内在转化生长因子-β和白细胞介素-4的影响下独立于白细胞介素-12促进Th1细胞的作用而发生。
