Regulation of TCR-mediated T cell activation by TNF-RII
Regulation of TCR-mediated T cell activation by TNF-RII
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DOI：
10.1189/jlb.0303112
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发表时间：
2003-10-01
影响因子：
5.5
通讯作者：
Wolf, HM
中科院分区：
文献类型：
--
作者：
Aspalter, RM;Eibl, MM;Wolf, HM
在本研究中，我们研究了肿瘤坏死因子受体II（TNF-RII）在通过T细胞受体（TCR）在抗原呈递细胞非依赖性系统中诱导的人T细胞活化中的作用。我们的研究结果证实，TNF-α与TNF-RII而不是TNF-RI的相互作用直接共刺激TCR介导的T细胞活化，从而增强T细胞增殖，T细胞活化标志物（CD 25，人白细胞抗原-DR，TNF-RII）的表达，以及细胞因子如干扰素-γ和TNF-α的分泌。与明确定义的共刺激分子CD 28相比，通过TNF-RII的共刺激在动力学、交联要求、所涉及的细胞内信号传导途径的冗余以及诱导白细胞介素（IL）-2，IL-10和IL-13分泌的能力方面显示出显著差异。此外，交联TNF-RII具有下调TCR/CD 28诱导的Ca++动员、IL-2 mRNA表达以及IL-2和IL-10分泌的能力。总之，我们的研究结果表明，TNF-RII在T细胞共刺激分子中起着独特的作用，因为TNF-RII连接可以对TCR依赖性信号传导产生积极和消极的影响。TNF-RII交联对邻近Ca++通量诱导的早期TCR信号传导事件具有抑制作用，最终导致T细胞细胞因子表达模式的调节。
In the present study, we investigated the role of tumor necrosis factor receptor II (TNF-RII) in human T cell activation induced via the T cell receptor (TCR) in an antigen-presenting cell-independent system. Our results confirm that interaction of TNF-alpha with TNF-RII but not TNF-RI is directly costimulatory to TCR-mediated T cell activation, thereby augmenting T cell proliferation, expression of T cell activation markers (CD25, human leukocyte antigen-DR, TNF-RII), and secretion of cytokines such as interferon-gamma and TNF-alpha. In contrast to the well-defined costimulatory molecule CD28, costimulation via TNF-RII showed significant differences in kinetics, requirement for cross-linking, redundancy of intracellular signaling pathways involved, and the capacity to induce interleukin (IL)-2, IL-10, and IL-13 secretion. In addition, cross-linking TNF-RII had the capacity to down-regulate TCR/CD28-induced Ca++ mobilization,, IL-2 mRNA expression, and IL-2 and IL-10 secretion. Taken together, our findings demonstrate that TNF-RII plays a unique role among the T cell costimulatory molecules, as TNF-RII ligation can have positive and negative effects on TCR-dependent signaling. TNF-RII cross-linking has an inhibitory effect on early TCR signaling events proximal to induction of Ca++ flux, which ultimately leads to modulation of the T cell cytokine pattern expressed.