Cucak Helena, Yrlid Ulf, Reizis Boris, Kalinke Ulrich, Johansson-Lindbom Bengt
Immunology Section, BMC D14, Lund University, Lund 22184, Sweden.
Immunity. 2009 Sep 18;31(3):491-501. doi: 10.1016/j.immuni.2009.07.005. Epub 2009 Sep 3.
T follicular helper (Tfh) cells represent a recently defined CD4(+) T cell subset characterized by the expression of the chemokine receptor CXCR5 and an enhanced ability to support B cells to mount antibody responses. Here, we demonstrate that lymph-node-resident CXCR5(+) Tfh cells and gut-homing integrin alpha(4)beta(7)-expressing T helper cells are generated as separate subsets in the gut-draining mesenteric lymph nodes. Type I interferon signaling in dendritic cells and in nonhematopoietic cells selectively stimulates Tfh cell development in response to antigen in conjunction with Toll-like receptor (TLR)3 or TLR4 agonists. Consistent with this, the ability of dendritic cells to produce the cytokine IL-6, required for in vivo Tfh differentiation, and antibody affinity maturation are both reduced in absence of type I interferon signaling. Thus, our results identify type I interferon as a natural adjuvant that selectively supports the generation of lymph node resident Tfh cells.
滤泡辅助性T（Tfh）细胞是最近定义的一种CD4(+) T细胞亚群，其特征在于表达趋化因子受体CXCR5，并具有增强的支持B细胞产生抗体反应的能力。在此，我们证明，驻留在淋巴结中的CXCR5(+) Tfh细胞和表达归巢至肠道的整合素α(4)β(7)的辅助性T细胞是在引流肠道的肠系膜淋巴结中作为不同的亚群产生的。树突状细胞和非造血细胞中的I型干扰素信号传导，与Toll样受体（TLR）3或TLR4激动剂联合作用，可选择性地刺激Tfh细胞在抗原刺激下的发育。与此一致的是，在缺乏I型干扰素信号传导的情况下，树突状细胞产生体内Tfh分化所需的细胞因子IL-6的能力以及抗体亲和力成熟度均降低。因此，我们的结果确定I型干扰素是一种天然佐剂，可选择性地支持淋巴结驻留Tfh细胞的产生。
