Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation.
Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation.
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DOI：
10.1096/fj.10-166843
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Jones SA
中科院分区：
文献类型：
--
作者：
Jones GW;Stumhofer JS;Foster T;Twohig JP;Hertzog P;Topley N;Williams AS;Hunter CA;Jenkins BJ;Wang EC;Jones SA
肿瘤坏死因子（TNF）样细胞因子（TL 1A）是一种T细胞共刺激因子，通过死亡受体3（DR 3）支持尼古丁诱导的活化。为了探索T细胞活化与TL 1A应答之间的关系，流式细胞术分析了静息和活化T细胞中DR 3的表达。在人CD 4 + T细胞中，DR 3在活化后迅速诱导，并由分泌白细胞介素（IL）-17的T细胞（Th 17）显著表达。来自野生型和DR 3缺陷型小鼠的脾T细胞显示，DR 3的TL 1A活化抑制来自初始T细胞的Th 17生成（在100 ng/ml TL 1A下为81±2.6%）。这种反应与抑制T细胞增殖无关。使用来自遗传修饰小鼠的中和抗体或T细胞，发现TL 1A对Th 17发育的抑制不依赖于IL-2、IL-27、γIFN、IFNAR 1和STAT 1。在次优TCR活化下，TL 1A继续阻断IL-17 A分泌，然而，TCR接合的降低的阈值现在与TL 1A驱动的增殖的增加有关。相反，完全定型的Th 17细胞显示出改变的TL 1A反应性，并且在不存在TCR共刺激的情况下支持T细胞IL-17 A表达的维持。因此，TL 1A在幼稚和效应T辅助细胞中协调独特的结果，这可能会影响外周隔室和炎症组织中Th 17细胞的增殖，分化和维持。琼斯湾，澳-地W.，Stumhofer，J.S.，福斯特，T.，Twohig，J.P.，Hertzog，P.，Topley，N.，威廉姆斯，A.美国，亨特角一、詹金斯，B。J.，Wang，中国山核桃E. C.是的，琼斯，S。A.初始和活化的T细胞显示对TL 1A的不同反应性，其影响Th 17的产生、维持和增殖。
Tumor necrosis factor (TNF)-like cytokine (TL1A) is a T-cell costimulator that bolsters cytokine-induced activation through death receptor 3 (DR3). To explore the relationship between T-cell activation and TL1A responsiveness, flow cytometry profiled DR3 expression in resting and activated T cells. In human CD4+ T cells, DR3 was induced rapidly following activation and expressed prominently by interleukin (IL)-17-secreting T cells (Th17). Splenic T cells from wild-type and DR3-deficient mice showed that TL1A activation of DR3 inhibits Th17 generation (81±2.6% at 100 ng/ml TL1A) from naive T cells. This response was not associated with suppression of T-cell proliferation. Using neutralizing antibodies or T cells derived from genetically modified mice, TL1A inhibition of Th17 development was found to be independent of IL-2, IL-27, γIFN, IFNAR1, and STAT1. Under suboptimal TCR activation, TL1A continued to block IL-17A secretion, however, the reduced threshold of TCR engagement was now linked with an increase in TL1A-driven proliferation. In contrast, fully committed Th17 cells displayed an altered TL1A responsiveness and in the absence of TCR costimulation supported the maintenance of T cell IL-17A expression. Consequently, TL1A orchestrates unique outcomes in naive and effector T-helper cells, which may affect the proliferation, differentiation and maintenance of Th17 cells in peripheral compartments and inflamed tissues.—Jones, G. W., Stumhofer, J. S., Foster, T., Twohig, J.P., Hertzog, P., Topley, N., Williams, A. S., Hunter, C. A., Jenkins, B. J., Wang, E. C. Y., Jones, S. A. Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation.
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