OX40-mediated memory T cell generation is TNF receptor-associated factor 2 dependent
OX40-mediated memory T cell generation is TNF receptor-associated factor 2 dependent
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DOI：
10.4049/jimmunol.171.11.5997
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发表时间：
2003-12-01
影响因子：
4.4
通讯作者：
Weinberg, AD
中科院分区：
文献类型：
--
作者：
Prell, RA;Evans, DE;Weinberg, AD
肿瘤坏死因子受体相关因子2（TRAF 2）是一种与OX 40胞质尾区相关的衔接蛋白，在OX 40介导的信号转导中发挥重要作用。为了研究TRAF 2在OX 40介导的Ag特异性记忆T细胞产生中的体内作用，我们将OVA特异性TCR转基因小鼠与TRAF 2显性阴性（TRAF 2 DN）小鼠交配。在体内TRAF 2 DN T细胞的Ag刺激和OX 40参与后，与野生型T细胞相比，长寿命的OVA特异性T细胞的数量和效应T细胞功能显著降低。我们还证明了CTLA-4在体内OX 40参与后下调，并且OX 40特异性TRAF 2 DN缺陷被CTLA-4阻断部分克服。这些数据提供了TRAF 2与OX 40介导的记忆T细胞扩增和存活相关的证据，并指出CTLA-4的下调是通过OX 40信号传导增强早期T细胞扩增的可能控制元件。
Tumor necrosis factor receptor-associated factor 2 (TRAF2), an adapter protein that associates with the cytoplasmic tail of OX40, may play a critical role in OX40-mediated signal transduction. To investigate the in vivo role of TRAF2 in OX40-mediated generation of Ag-specific memory T cells, we bred OVA-specific TCR transgenic mice to TRAF2 dominant-negative (TRAF2 DN) mice. Following Ag stimulation and OX40 engagement of TRAF2 DN T cells in vivo, the number of long-lived OVA-specific T cells and effector T cell function was dramatically reduced when compared with wild-type T cells. We also demonstrate that CTLA-4 is down-regulated following OX40 engagement in vivo and the OX40-specific TRAF2 DN defect was partially overcome by CTLA-4 blockade in vivo. The data provide evidence that TRAF2 is linked to OX40-mediated memory T cell expansion and survival, and point to the down-regulation of CTLA-4 as a possible control element to enhance early T cell expansion through OX40 signaling.