Akaishi H, Takeda K, Kaisho T, Shineha R, Satomi S, Takeda J, Akira S
Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Japan.
Int Immunol. 1998 Nov;10(11):1747-51. doi: 10.1093/intimm/10.11.1747.
Stat3, a member of signal transducers and activators of transcription (STAT), is activated by a variety of cytokines. Recently, mice lacking Stat3 specifically in T cells have been generated and shown to be defective in IL-6-induced proliferation due to the impairment in IL-6-mediated prevention of apoptosis. In the present study, we show that Stat3-deficient T cells are partially defective in IL-2-induced proliferation. Stat3-deficient T cells show impaired IL-2-mediated IL-2 receptor (IL-2R) alpha chain expression. When Stat3-deficient T cells are stimulated with high-dose IL-2, these T cells express IL-2Ralpha and proliferate to similar extents as wild-type T cells. These demonstrate that Stat3 activation is required for efficient T cell proliferation by IL-2 through IL-2Ralpha induction. Taken together, these findings demonstrate that Stat3 activation in T cells is responsible for IL-2- and IL-6-induced proliferation through distinct mechanisms.
信号转导与转录激活因子（STAT）家族成员Stat3可被多种细胞因子激活。最近，研究人员构建了T细胞中特异性缺失Stat3的小鼠，结果显示这些小鼠因IL-6介导的细胞凋亡预防功能受损，在IL-6诱导的增殖过程中存在缺陷。在本研究中，我们发现Stat3缺陷型T细胞在IL-2诱导的增殖过程中存在部分缺陷。Stat3缺陷型T细胞表现出IL-2介导的IL-2受体（IL-2R）α链表达受损。当用高剂量IL-2刺激Stat3缺陷型T细胞时，这些T细胞表达IL-2Rα，并增殖至与野生型T细胞相似的程度。这些结果表明，Stat3激活是IL-2通过诱导IL-2Rα实现高效T细胞增殖所必需的。综上所述，这些发现表明T细胞中的Stat3激活通过不同机制负责IL-2和IL-6诱导的增殖。
