OX40-OX40 ligand interaction through T cell-T cell contact contributes to CD4 T cell longevity
OX40-OX40 ligand interaction through T cell-T cell contact contributes to CD4 T cell longevity
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DOI：
10.4049/jimmunol.176.10.5975
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发表时间：
2006-05-15
影响因子：
4.4
通讯作者：
Ishii, Naoto
中科院分区：
文献类型：
--
作者：
Soroosh, Pejman;Ine, Shouji;Ishii, Naoto
通过初始CD 4 T细胞上的OX 40共刺激受体的信号对于完全成熟的CD 4 T细胞活化和CD 4记忆T细胞的产生是必不可少的。由于OX 40的配体主要由APC表达，包括活化的B细胞、树突状细胞和朗格汉斯细胞，因此OX 40-OX 40配体（OX 40 L）相互作用被认为参与T细胞-APC相互作用。虽然已有报道表明OX 40 L在T细胞上表达，但其在T细胞上表达的功能意义尚不清楚。在这项研究中，我们证明，银刺激诱导的表面表达和转录水平的CD 4 T细胞中的OX 40 L的增加。在与表达OX 40的T细胞接触后，CD 4 T细胞上OX 40 L的细胞表面表达显著下调，表明OX 40-OX 40 L结合通过新的T细胞-T细胞相互作用发生。为了研究这种现象的功能，我们研究了用Ag攻击时OX 40 L缺陷的CD 4 T细胞的增殖反应和存活。体外研究表明，与野生型CD 4 T细胞相比，CD 3诱导的OX 40 L缺陷型CD 4 T细胞增殖明显减少。当在Ag刺激后使用TCR转基因CD 4 T细胞时，0X 40 L缺陷型T细胞的存活受损。此外，我们表明，在抗原刺激后，转移到野生型和亚致死剂量照射的受体小鼠后，OX 40 L缺陷型CD 4 T细胞的存活率低于野生型细胞。综上所述，我们的研究结果表明，表达OX 40 L的T细胞具有通过T细胞-T细胞回路提供OX 40信号的自主机制，为维持CD 4 T细胞寿命创造了额外的机制。
Signals through the OX40 costimulatory receptor on naive CD4 T cells are essential for full-fledged CD4 T cell activation and the 14 generation of CD4 memory T cells. Because the ligand for OX40 is mainly expressed by APCs, including activated B cells, dendritic cells, and Langerhans cells, the OX40-OX40 ligand (OX40L) interaction has been thought to participate in T cell-APC interactions tions. Although several reports have revealed the expression of OX40L on T cells, the functional significance of its expression on them is still unclear. In this study, we demonstrate that Ag stimulation induced an increase in the surface expression and transcript levels of OX40L in CD4 T cells. Upon contact with OX40-expressing T cells, the cell surface expression of OX40L on CD4 T cells was markedly down-regulated, suggesting that OX40-OX40L binding occurs through a novel T cell-T cell interaction. To investigate the function of this phenomenon, we examined the proliferative response and survival of OX40L-deficient CD4 T cells when challenged with Ag. In vitro studies demonstrated markedly less CD3-induced proliferation of OX40L-deficient CD4 T cells compared with wild-type CD4 T cells. When using TCR transgenic CD4 T cells upon Ag stimulation, survival of OX40L-deficient T cells was impaired. Furthermore, we show that upon antigenic stimulation, fewer OX40L-deficient CD4 T cells than wild-type cells survived following transfer into wild-type and sublethally irradiated recipient mice. Taken together, our findings indicate that OX40L-expressing T cells have an autonomous machinery that provides OX40 signals through a T cell-T cell circuit, creating an additional mechanism for sustaining CD4 T cell longevity.