Influence of CCR7 ligand DNA preexposure on the magnitude and duration of immunity.
Influence of CCR7 ligand DNA preexposure on the magnitude and duration of immunity.
复制标题
DOI：
10.1016/s0042-6822(03)00199-5
复制
发表时间：
2003-07
期刊：
影响因子：
3.7
通讯作者：
Yunsang Lee;S. Eo;R. Rouse;B. Rouse
中科院分区：
文献类型：
--
作者：
Yunsang Lee;S. Eo;R. Rouse;B. Rouse
CC趋化因子受体（CCR）7配体CCL21和CCL19最近被描述为建立在次级淋巴组织中启动最佳免疫反应所需的微环境的基本要素。在本研究中，我们从动力学角度研究了幼稚 DO11.10 TCR 转基因 CD4+ T 细胞（OVA323-339 肽特异性）过继转移到正常 BALB/c 小鼠中的初级反应，给予编码 CCR7 配体的质粒 DNA。 CCR7 配体 DNA 受体中 CD4+ Tg-T 细胞的初级反应发生得更迅速，达到的水平高于载体对照中观察到的水平。与增强的特异性免疫一致，CCR7配体受体中的T细胞群在Ag刺激后经历了更多的体内细胞分裂，并且更高比例的Ag特异性T细胞表达激活表型。此外，初始 CD4+ T 细胞增强的初级反应似乎是通过影响引流淋巴结中 CD11c+ 树突状细胞的迁移和成熟而发挥作用。此外，在用病毒对单纯疱疹病毒免疫小鼠进行粘膜攻击后，那些在启动期间接受CCL21或CCL19的小鼠在淋巴结和感染部位含有更高频率的响应CD4 T细胞。此外，CCL21 和 CCL19 治疗的小鼠在攻击后表现出较轻的疾病和更好的存活率。我们的结果根据 CCR7 配体预免疫与改进疫苗的相关性进行了讨论。
The CC chemokine receptor (CCR) 7 ligands CCL21 and CCL19 were recently described as essential elements for establishing the microenvironment needed to initiate optimal immune responses in secondary lymphoid tissues. In the present study we have kinetically investigated the primary responses of naive DO11.10 TCR-transgenic CD4+ T cells (OVA323-339 peptide specific) adoptively transferred into normal BALB/c mice given plasmid DNA encoding CCR7 ligands. The primary responses of CD4+ Tg-T cells in CCR7 ligand DNA recipients occurred more promptly, reaching levels higher than those observed in vector controls. In line with enhanced specific immunity, the T-cell population in CCR7 ligand recipients underwent more in vivo cell division following Ag stimulation, and a higher percentage of Ag-specific T cells expressed an activation phenotype. Moreover, the enhanced primary responses of naive CD4+ T cells appeared to act via affects on migration and maturation of CD11c+ dendritic cells in the draining lymph nodes. In addition following mucosal challenge of herpes simplex virus-immune mice with virus, those that had received CCL21 or CCL19 during priming contained a higher frequency of responding CD4 T cells in lymph nodes and the site of infection. Moreover, CCL21- and CCL19-treated mice showed less severe disease and better survival following challenge. Our results are discussed in terms of the relevance of CCR7 ligand preimmunization to improve vaccine.