Chakarov Svetoslav, Fazilleau Nicolas
Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
EMBO Mol Med. 2014 May;6(5):590-603. doi: 10.1002/emmm.201403841.
To be effective, protein priming must induce the development of a distinct lineage of CD4(+) T cells named T follicular helper (Tfh) cells, which regulate the differentiation of high-affinity memory B cells and long-lived plasma cells. In this context, we tested how adjuvantation with CpG, the Toll-like receptor 9 agonist used in clinics, contributes to antigen-specific T-cell-dependent B-cell responses in vivo. We found that addition of CpG to other vaccine adjuvant increased the differentiation of antigen-specific Tfh cells without changing the overall magnitude of the T-cell response. This phenomenon correlated with an enhancement of the germinal centre reaction, antigen-specific plasma cells and circulating antibodies. We comprehensively demonstrated that, in addition to the classical Tfh-cell differentiation mediated by conventional DC, the promoting effect due to CpG was orchestrated in vivo by antigen presentation and IL-6 secreted by monocyte-derived dendritic cells (DC) as shown in their absence. Thus, while conventional DC initiate T-cell responses, targeting monocyte-derived DC specifically enhances the Tfh programme needed to regulate high-affinity B-cell protection in vivo.
为了发挥作用，蛋白质启动必须诱导一种名为滤泡辅助性T细胞（Tfh细胞）的独特CD4(+) T细胞谱系的发育，该细胞谱系调节高亲和力记忆B细胞和长寿浆细胞的分化。在此背景下，我们测试了临床上使用的Toll样受体9激动剂CpG作为佐剂如何在体内促进抗原特异性T细胞依赖性B细胞反应。我们发现，在其他疫苗佐剂中添加CpG可增加抗原特异性Tfh细胞的分化，而不改变T细胞反应的总体强度。这一现象与生发中心反应、抗原特异性浆细胞和循环抗体的增强相关。我们全面证明，除了传统树突状细胞（DC）介导的经典Tfh细胞分化外，如在缺乏单核细胞衍生树突状细胞（DC）时所示，CpG的促进作用是由单核细胞衍生树突状细胞（DC）呈递的抗原和分泌的白细胞介素-6在体内精心安排的。因此，虽然传统DC启动T细胞反应，但特异性靶向单核细胞衍生DC可增强体内调节高亲和力B细胞保护所需的Tfh程序。
