Rogge L, D'Ambrosio D, Biffi M, Penna G, Minetti L J, Presky D H, Adorini L, Sinigaglia F
Roche Milano Ricerche, Milan, Italy.
J Immunol. 1998 Dec 15;161(12):6567-74.
Type I IFNs (IFN-alpha/beta), in addition to IL-12, have been shown to play an important role in the differentiation of human, but not mouse, Th cells. We show here that IFN-alpha/beta act directly on human T cells to drive Th1 development, bypassing the need for IL-12-induced signaling, whereas IFN-alpha cannot substitute IL-12 for mouse Th1 development. The molecular basis for this species specificity is that IFN-alpha/beta activate Stat4 in differentiating human, but not mouse, Th cells. Unlike IL-12, which acts only on Th1 cells, IFN-alpha/beta can activate Stat4 not only in human Th1, but also in Th2 cells. However, restimulation of human Th2 lines and clones in the presence of IFN-alpha does not induce the production of IFN-gamma. These results suggest that activation of Stat4, which is necessary for the differentiation of naive T cells into polarized Th1 cells, is not sufficient to induce phenotype reversal of human Th2 cells.
I型干扰素（IFN-α/β），除白细胞介素-12外，已被证明在人类而非小鼠的Th细胞分化中发挥重要作用。我们在此表明，IFN-α/β直接作用于人类T细胞以驱动Th1细胞发育，绕过了对白细胞介素-12诱导信号的需求，而IFN-α不能替代白细胞介素-12用于小鼠Th1细胞发育。这种物种特异性的分子基础是IFN-α/β在分化中的人类而非小鼠Th细胞中激活信号转导和转录激活因子4（Stat4）。与仅作用于Th1细胞的白细胞介素-12不同，IFN-α/β不仅能在人类Th1细胞中激活Stat4，还能在Th2细胞中激活Stat4。然而，在IFN-α存在的情况下对人类Th2细胞系和克隆进行再刺激并不会诱导γ干扰素的产生。这些结果表明，Stat4的激活对于初始T细胞分化为极化的Th1细胞是必要的，但不足以诱导人类Th2细胞的表型逆转。
