TNFRI is a positive T‐cell costimulatory molecule important for the timing of cytokine responses
TNFRI is a positive T‐cell costimulatory molecule important for the timing of cytokine responses
复制标题
TNFRI 是一种阳性 T 细胞共刺激分子，对于细胞因子反应的时机很重要
作者：
Maria Evangelidou;V. Tseveleki;Sotiris;L. Probert
肿瘤坏死因子（TNF）和TNF受体I（TNFRI）缺陷型小鼠对启动有抵抗力，并在自身免疫性疾病的范例中显示出疾病的延迟消退，但TNF/TNFRI信号传导对T细胞活化和效应器应答的贡献尚未确定。在这项研究中，我们研究了TNFRI在T细胞受体（TCR）介导的T细胞活化中的作用，在体外和体内使用CD 3+富集的原代T细胞和TNFRI缺乏的小鼠。与野生型（WT）细胞相比，TCR接合后，TNFRI敲除（KO）T细胞显示出显著延迟的增殖、细胞分裂、白细胞介素2（IL-2）和IL-2受体α链（CD 25）mRNA的上调以及CD 25的细胞表面表达。因此，WT和TNFRI KO细胞分别在48和72小时显示出相等的增殖峰。TNFRI KO小鼠还出现了对卵清蛋白的缺陷性原发性T细胞应答和对恶唑酮（4-乙氧基亚甲基-2-苯基-2-恶唑啉-5-酮）的急性接触性超敏反应。然而，与WT细胞相比，在体外由TCR接合刺激96小时的TNFRI KO脾细胞产生显著更高的细胞内水平的干扰素-γ（IFN-γ）、IL-2和TNF-α，但不产生IL-17，这与它们在该时间点相对更高的增殖速率相关。此外，与WT相比，TCR刺激的富含CD 3+的TNFRI KO T细胞显示出类似的更高的IFN-γ和IL-2的产生和分泌，表明TNFRI介导的细胞因子调节可能涉及T细胞自主效应。我们的研究结果表明，TNFRI作为一种阳性T细胞共刺激分子具有新的作用，对于及时的T细胞活化和效应细胞因子产生以及小鼠原发性免疫应答的发展非常重要。
Tumor necrosis factor (TNF)‐ and TNF receptor I (TNFRI)‐deficient mice are resistant to initiation and show delayed resolution of disease in paradigms of autoimmune disease, but the contribution of TNF/TNFRI signaling to T‐cell activation and effector responses has not been determined. In this study, we investigated the role of TNFRI in T‐cell receptor (TCR)‐mediated T‐cell activation in vitro and in vivo using CD3+‐enriched primary T cells and mice deficient in TNFRI. Following TCR engagement, TNFRI knockout (KO) T cells showed significantly delayed proliferation, cell division, upregulation of interleukin 2 (IL‐2) and IL‐2 receptor α chain (CD25) mRNA and cell‐surface expression of CD25 compared with wild‐type (WT) cells. Thus, WT and TNFRI KO cells showed equivalent proliferation peaks at 48 and 72 h, respectively. TNFRI KO mice also developed a defective primary T‐cell response to ovalbumin and an acute contact hypersensitivity response to oxazolone (4‐ethoxymethylene‐2‐phenyl‐2‐oxazolin‐5‐one). However, TNFRI KO splenocytes that were stimulated by TCR engagement in vitro for 96 h produced significantly higher intracellular levels of interferon‐γ (IFN‐γ), IL‐2 and TNF‐α, but not IL‐17, compared with WT cells, in correlation with their relatively higher proliferation rate at this time point. Further, TCR‐stimulated CD3+‐enriched TNFRI KO T cells showed similarly higher production and secretion of IFN‐γ and IL‐2 compared with WT, suggesting that TNFRI‐mediated cytokine regulation might involve a T‐cell autonomous effect. Our results show a novel role for TNFRI as a positive T‐cell costimulatory molecule that is important for timely T‐cell activation and effector cytokine production and the development of primary immune responses in mice.
影响因子：
13
作者：
So, Takanori;Lee, Seung-Woo;Croft, Michael
通讯作者：
Croft, Michael
影响因子：
32.4
作者：
Rogers, PR;Song, JX;Croft, M
通讯作者：
Croft, M
影响因子：
4.3
作者：
Suvannavejh, GC;Lee, HO;Miller, SD
通讯作者：
Miller, SD