Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses.
Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses.
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DOI：
10.4049/jimmunol.161.12.6510
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发表时间：
1998-12
影响因子：
4.4
通讯作者：
I. Gramaglia;A. Weinberg;M. Lemon;M. Croft
中科院分区：
文献类型：
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作者：
I. Gramaglia;A. Weinberg;M. Lemon;M. Croft
Ox-40 和 Ox-40 配体 (Ox-40L) 被认为参与 T 细胞-APC 相互作用。然而，它们在 T 细胞反应中的确切作用尚不清楚。使用表达 Ox-40L 和/或 B7-1 的成纤维细胞转染子以及来自 TCR 转基因小鼠的 CD4 细胞，我们研究了 Ox-40 信号传导对银鸽细胞色素 c 初级反应的影响。初始 CD4 细胞上的 Ox-40 表达在激活后 2 至 3 天达到峰值，并在 4 至 5 天后消失。与 B7-1 不同，具有 Ox-40L 的 APC 促进初始 T 细胞的部分激活，并分泌一些 IL-2，但无法增强增殖。共表达 Ox-40L 与 B7-1 的 APC 诱导大量 IL-2 并促进持续数天的增殖反应。幼稚 T 细胞激活后 5 天取出的效应细胞在 4 小时内重新表达 Ox-40，并对表达 Ox-40L 的 APC 产生强烈反应，而 B7-1 几乎没有作用。 Ox-40L 和 B7-1 之间也存在协同作用，主要是 IL-2 升高，尽管 IL-4 和 IL-5 也上调。最显着的作用是对效应 T 细胞增殖的影响，这种增殖持续高水平长达 4 天，在缺乏 Ox-40 信号的情况下，此时几乎没有明显的增殖。这些数据表明，Ox-40/Ox-40L 相互作用在初始激活事件后起作用，以延长克隆扩增并增强效应细胞因子分泌，并且可能参与促进长寿命的初级 CD4 反应。
Ox-40 and Ox-40 ligand (Ox-40L) are thought to be involved in T cell-APC interactions. However, their exact role in T cell responses is undefined. Using fibroblast transfectants expressing Ox-40L and/or B7-1, and CD4 cells from TCR transgenic mice, we investigated the effect of Ox-40 signaling on primary responses to the Ag pigeon cytochrome c. Ox-40 expression on naive CD4 cells peaked 2 to 3 days after activation, and was lost by 4 to 5 days. APCs with Ox-40L promoted partial activation of naive T cells with some IL-2 secretion, but were unable to enhance proliferation, unlike those with B7-1. APCs coexpressing Ox-40L with B7-1 induced large quantities of IL-2 and promoted proliferative responses that persisted for several days. Effector cells taken 5 days after naive T cell activation reexpressed Ox-40 within 4 h and responded strongly to APCs expressing Ox-40L, whereas B7-1 had little effect. Synergy was also seen between Ox-40L and B7-1, with primarily IL-2 being elevated, although IL-4 and IL-5 were also up-regulated. The most striking action was on effector T cell proliferation, which continued at high levels for up to 4 days, with little proliferation evident at this time in the absence of Ox-40 signals. These data suggest that Ox-40/Ox-40L interactions act after initial activation events to prolong clonal expansion and enhance effector cytokine secretion, and may be involved in promoting long-lived primary CD4 responses.