Dendritic cell expression of OX40 ligand acts as a costimulatory, not polarizing, signal for optimal th2 priming and memory induction in vivo
Dendritic cell expression of OX40 ligand acts as a costimulatory, not polarizing, signal for optimal th2 priming and memory induction in vivo
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DOI：
10.4049/jimmunol.179.6.3515
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发表时间：
2007-09-15
影响因子：
4.4
通讯作者：
MacDonald, Andrew S.
中科院分区：
文献类型：
--
作者：
Jenkins, Stephen J.;Perona-Wright, Georgia;MacDonald, Andrew S.
共刺激串扰可以发生在多个细胞水平，以增强Th反应的扩展和极化。虽然OX 40 L配体（OX 40 L）被认为在Th 2发育中起关键作用，但该分子的关键细胞来源尚未确定。在这项研究中，我们证明，OX 40 L的启动树突状细胞（DC）的表达是一个基本的要求，在体内的初级和记忆性Th 2反应的最佳诱导。对由OX 40 L缺陷型DC引发的残余Th 2应答的动力学分析表明未能刺激T细胞的适当扩增和/或存活，而不是不能自身扩增。对OX 40 L的依赖主要是由于通过OX 40提供信号而不是向DC提供逆行信号。从机制上讲，在不存在OX 40 L的情况下受损的Th 2引发不是由于过度调节，因为没有证据表明调节细胞群的扩增或功能增加，通过IL-10产生的抑制，或对二次攻击的低反应性。这些数据定义了DC衍生的OX 40 L在体内诱导和发展Th 2应答中的关键作用。
Costimulatory cross-talk can occur at multiple cellular levels to potentiate expansion and polarization of Th responses. Although OX40L ligand (OX40L) is thought to play a key role in Th2 development, the critical cellular source of this molecule has yet to be identified. In this study, we demonstrate that OX40L expression by the initiating dendritic cell (DC) is a fundamental requirement for optimal induction of primary and memory Th2 responses in vivo. Analysis of the kinetics of the residual Th2 response primed by OX40L-deficient DC suggested a failure to stimulate appropriate expansion and/or survival of T cells, rather than an inability to polarize per se. The dependence upon OX40L was predominantly due to the provision of signaling through OX40 rather than retrograde signaling to the DC. Mechanistically, impaired Th2 priming in the absence of OX40L was not due to exaggerated regulation because there was no evidence of increased expansion or function of regulatory cell populations, suppression through IL-10 production, or hyporesponsiveness to secondary challenge. These data define a critical role for DC-derived OX40L in the induction and development of Th2 responses in vivo.