Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo.
Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo.
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通过B细胞表达的OX40L共刺激足以确定体内原代CD4细胞膨胀和Th2细胞因子分泌的程度。
DOI：
10.1084/jem.20021290
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发表时间：
2003-04-07
影响因子：
15.3
通讯作者：
Bradley, LM
中科院分区：
文献类型：
--
作者：
Linton, PJ;Bautista, B;Biederman, E;Bradley, ES;Harbertson, J;Kondrack, RM;Padrick, RC;Bradley, LM
效应型和记忆型CD4细胞群的发育既依赖于T细胞受体(TCR)与多肽/主要组织相容性复合体(MHC)II类复合体的结合，也依赖于共刺激分子与抗原提呈细胞(APC)上的对抗性受体的连接。我们先前的研究表明，与APC的持续相互作用对于CD4细胞的最佳扩增和分泌与Th2细胞相关的细胞因子的效应器的发展至关重要。利用TCR转基因CD4细胞的过继转移模型，我们现在表明，在B细胞缺陷小鼠中，启动的CD4细胞的反应被流产，但在转移激活的B细胞后完全恢复。尽管B细胞具有分泌多种细胞因子的能力，包括IL-4，但我们无法区分B细胞分泌的细胞因子的作用。然而，通过OX40L/OX40通路的B细胞共刺激是必需的，该通路与CD4细胞的扩增、存活和Th2的发育有关。OX40L缺乏的受者Th2反应受损，但Th1反应不受影响，而OX40L充足的B细胞可恢复正常反应。结果提示，在B细胞上没有OX40L结合的情况下，CD4细胞对多种蛋白Ag的反应将由Th1细胞因子主导。这些数据对实现CD4亚群最佳启动的策略具有重要意义。
The development of effector and memory CD4 cell populations depends upon both T cell receptor (TCR) engagement of peptide/major histocompatibility complex (MHC) class II complexes and ligation of costimulatory molecules with counter receptors on antigen-presenting cells (APCs). We showed previously that sustained interactions with APCs could be crucial for optimal expansion of CD4 cells and for development of effectors that secrete cytokines associated with Th2 cells. Using an adoptive transfer model with TCR transgenic CD4 cells, we now show that responses of CD4 cells primed in B cell–deficient mice become aborted, but are fully restored upon the transfer of activated B cells. Although B cells have the capacity to secrete multiple cytokines that could affect CD4 priming, including IL-4, we were unable to distinguish a role for cytokines that are secreted by B cells. However, B cell costimulation via the OX40L/OX40 pathway that has been implicated in CD4 cell expansion, survival, and Th2 development was required. Th2 but not Th1 responses were impaired in OX40L-deficient recipients and normal responses were restored with OX40L sufficient B cells. The results suggest that without engagement of OX40L on B cells, CD4 cell responses to many protein Ag would be dominated by Th1 cytokines. These data have important implications for strategies to achieve optimal priming of CD4 subsets.
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