The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion
The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion
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DOI：
10.4049/jimmunol.165.6.3043
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发表时间：
2000-09-15
影响因子：
4.4
通讯作者：
Croft, M
中科院分区：
文献类型：
--
作者：
Gramaglia, I;Jember, A;Croft, M
共刺激受体OX 40最近被证明参与了对几种确定的抗原的初级CD 4应答，然而，迄今为止，关于OX 40的作用机制的信息很少，例如它是否调节T细胞数量、反应性或两者，以及它是否有助于诱导长期T细胞应答。与激动剂抗体OX 40，并通过跟踪Ag-特异性TCR转基因T细胞在体内，我们表明，OX 40的连接诱导的克隆扩增和生存的CD 4细胞在初级反应，并导致随着时间的推移积累更多的记忆细胞。值得注意的是，来自通过基因靶向产生的小鼠的OX 40缺陷型T细胞在活化的初始阶段分泌IL-2并正常增殖，但在初级应答的后期阶段不能维持这种状态，表现出随时间推移存活率降低。缺乏OX 40的小鼠在体内主要反应后期仅产生低频率的Ag特异性CD 4细胞，并且产生显著较低频率的存活记忆细胞。这些结果证明0X 40 - 0X 40 L相互作用控制原代T细胞扩增和保留大量Ag特异性T细胞的能力。通过这种方式，OX 40信号促进更多数量的T细胞随着时间的推移而存活，并控制记忆T细胞库的大小。
The costimulatory receptor OX40 has recently been shown to be involved in primary CD4 responses to several defined Ags, However, to date there has been little information regarding the mechanism of action of OX40, such as whether it regulates T cell numbers, reactivity, or both, and whether it contributes to induction of long-term T cell responses. With an agonist Ab to OX40, and by tracking Ag-specific TCR transgenic T cells in vivo, we show that ligation of OX40 induces clonal expansion and survival of CD4 cells during primary responses, and results in the accumulation of greater numbers of memory cells with time. Significantly, OX40-deficient T cells, from mice generated by gene targeting, secrete IL-2 and proliferate normally during the initial period of activation, but cannot sustain this during the latter phases of the primary response, exhibiting decreased survival over time. Mice lacking OX40 develop only low frequencies of Ag-specific CD4 cells late in primary responses in vivo and generate dramatically lower frequencies of surviving memory cells. These results demonstrate that OX40-OX40L interactions control primary T cell expansion and the ability to retain high numbers of Ag-specific T cells. In this way, OX40 signals promote survival of greater numbers of T cells with time and control the size of the memory T cell pool.