Department of Haematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Clin Exp Immunol. 2010 Jun;160(3):479-88. doi: 10.1111/j.1365-2249.2010.04089.x. Epub 2010 Feb 2.
T helper type 1 (Th1)-type polarization plays a critical role in the pathophysiology of acute graft-versus-host disease (aGVHD). The differentiation of T cells into this subtype is dictated by the nature of the donor naive CD4(+) T cell-host antigen presenting cell (APC) interaction. Suppressors of cytokine signalling (SOCS) are a family of molecules that act as negative regulators for cytokine signalling, which regulate the negative cytokine signalling pathway through inhibiting the cytokine-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Studies have shown that SOCS proteins are key physiological regulators of both innate and adaptive immunity. These molecules are essential for T cell development and differentiation. SOCS-3 can inhibit polarization to Th1 and contribute to polarization to Th2. In this study, we found that interleukin (IL)-2 pre-incubation of C57BL/6 naive CD4(+) T cells could up-regulate the expression of SOCS-3. Naive CD4(+) T cells constitutively expressed low levels of SOCS-3 mRNA. SOCS-3 mRNA began to rise after 4 h, and reached peak level at 6 h. At 8 h it began to decrease. High expression of SOCS-3 mRNA induced by IL-2 could inhibit the proliferation of naive CD4(+) T cells following stimulation with allogeneic antigen. IL-2-induced high SOCS-3 expression in naive CD4(+) T cells could inhibit polarization to Th1 with stimulation of allogeneic antigens. We have demonstrated that IL-2-induced high SOCS-3 expression in naive CD4(+) T cells could reduce the incidence of aGVHD between major histocompatibility complex (MHC) completely mismatched donor and host when high SOCS3 expression of CD4(+)T cells encounter allogeneic antigen in time. These results show that IL-2-induced high SOCS-3 expression can inhibit aGVHD through inhibiting proliferation and polarization to Th1 with the stimulation of allogeneic antigen.
辅助性 T 细胞 1 型（Th1）极化在急性移植物抗宿主病（aGVHD）的病理生理学中起着关键作用。T 细胞向这种亚型的分化是由供体幼稚 CD4+T 细胞与宿主抗原呈递细胞（APC）相互作用的性质决定的。细胞因子信号转导抑制物（SOCS）是一类作为细胞因子信号转导负调节剂的分子，通过抑制细胞因子诱导的 Janus 激酶/信号转导和转录激活因子（JAK/STAT）途径来调节负细胞因子信号通路。研究表明，SOCS 蛋白是固有和适应性免疫的关键生理调节剂。这些分子对于 T 细胞的发育和分化是必不可少的。SOCS-3 可以抑制 Th1 极化，并有助于 Th2 极化。在这项研究中，我们发现白细胞介素（IL）-2 孵育 C57BL/6 幼稚 CD4+T 细胞可以上调 SOCS-3 的表达。幼稚 CD4+T 细胞持续表达低水平的 SOCS-3 mRNA。SOCS-3 mRNA 在 4 小时后开始上升，6 小时达到峰值。8 小时开始下降。IL-2 诱导的 SOCS-3 mRNA 的高表达可抑制同种抗原刺激后幼稚 CD4+T 细胞的增殖。IL-2 诱导的幼稚 CD4+T 细胞中 SOCS-3 的高表达可抑制同种抗原刺激后的 Th1 极化。我们已经证明，IL-2 诱导的幼稚 CD4+T 细胞中 SOCS-3 的高表达可以降低主要组织相容性复合物（MHC）完全错配供体和宿主之间 aGVHD 的发生率，当 CD4+T 细胞中的 SOCS3 表达遇到同种抗原时。这些结果表明，IL-2 诱导的 SOCS-3 高表达通过抑制同种抗原刺激下的增殖和 Th1 极化来抑制 aGVHD。
