Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers.
Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers.
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DOI：
10.1084/jem.190.8.1115
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发表时间：
1999-10-18
期刊：
影响因子：
--
通讯作者：
Lane P
中科院分区：
文献类型：
--
作者：
Walker LS;Gulbranson-Judge A;Flynn S;Brocker T;Raykundalia C;Goodall M;Förster R;Lipp M;Lane P
通过可溶性竞争物细胞毒性T淋巴细胞相关分子4-免疫球蛋白G1融合蛋白（CTLA 4-IG）使小鼠缺乏CD 28信号传导，不能上调体内OX 40表达或在免疫后形成生发中心。这与白细胞介素4产生受损和CD 4 T细胞上缺乏CXC趋化因子受体（CXCR）5（一种与迁移到B卵泡相关的趋化因子受体）有关。在CTLA 4-IG转基因小鼠中，通过共注射抗CD 28的激动性单克隆抗体恢复了生发中心的形成，但如果通过同时注射OX 40-IG融合蛋白来中断OX 40相互作用，则这基本上被抑制。这些数据表明，在引发时CD 4 T细胞的CD 28依赖性OX 40连接与CXCR 5表达的上调以及T细胞迁移到B细胞区域以支持生发中心形成有关。
Mice rendered deficient in CD28 signaling by the soluble competitor, cytotoxic T lymphocyte–associated molecule 4–immunoglobulin G1 fusion protein (CTLA4-Ig), fail to upregulate OX40 expression in vivo or form germinal centers after immunization. This is associated with impaired interleukin 4 production and a lack of CXC chemokine receptor (CXCR)5 on CD4 T cells, a chemokine receptor linked with migration into B follicles. Germinal center formation is restored in CTLA4-Ig transgenic mice by coinjection of an agonistic monoclonal antibody to CD28, but this is substantially inhibited if OX40 interactions are interrupted by simultaneous injection of an OX40-Ig fusion protein. These data suggest that CD28-dependent OX40 ligation of CD4 T cells at the time of priming is linked with upregulation of CXCR5 expression, and migration of T cells into B cell areas to support germinal center formation.