Dahlgren Madelene W, Gustafsson-Hedberg Tobias, Livingston Megan, Cucak Helena, Alsén Samuel, Yrlid Ulf, Johansson-Lindbom Bengt
Immunology Section, Lund University, 221 84 Lund, Sweden; and.
Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
J Immunol. 2015 Jun 1;194(11):5187-99. doi: 10.4049/jimmunol.1401938. Epub 2015 Apr 27.
Development of long-lived humoral immunity is dependent on CXCR5-expressing T follicular helper (Tfh) cells, which develop concomitantly to effector Th cells that support cellular immunity. Conventional dendritic cells (cDCs) are critical APCs for initial priming of naive CD4(+) T cells but, importantly, also provide accessory signals that govern effector Th cell commitment. To define the accessory role of cDCs during the concurrent development of Tfh and effector Th1 cells, we performed high-dose Ag immunization in conjunction with the Th1-biased adjuvant polyinosinic:polycytidylic acid (pI:C). In the absence of cDCs, pI:C failed to induce Th1 cell commitment and IgG2c production. However, cDC depletion did not impair Tfh cell differentiation or germinal center formation, and long-lived IgG1 responses of unaltered affinity developed in mice lacking cDCs at the time point for immunization. Thus, cDCs are required for the pI:C-driven Th1 cell fate commitment but have no crucial accessory function in relation to Tfh cell differentiation.
长寿体液免疫的发展依赖于表达CXCR5的滤泡辅助性T细胞（Tfh），这些细胞与支持细胞免疫的效应性Th细胞同时发育。传统树突状细胞（cDC）是初始激活幼稚CD4(+) T细胞的关键抗原呈递细胞（APC），但重要的是，它们还提供调控效应性Th细胞分化的辅助信号。为了确定cDC在Tfh和效应性Th1细胞同时发育过程中的辅助作用，我们结合偏向Th1的佐剂聚肌苷酸:聚胞苷酸（pI:C）进行了高剂量抗原免疫。在没有cDC的情况下，pI:C未能诱导Th1细胞分化和IgG2c产生。然而，cDC缺失并不损害Tfh细胞分化或生发中心形成，并且在免疫时间点缺乏cDC的小鼠中产生了亲和力未改变的长寿IgG1反应。因此，cDC是pI:C驱动的Th1细胞命运分化所必需的，但在Tfh细胞分化方面没有关键的辅助功能。
