Yang Rui, Masters April R, Fortner Karen A, Champagne Devin P, Yanguas-Casás Natalia, Silberger Daniel J, Weaver Casey T, Haynes Laura, Rincon Mercedes
Department of Medicine/Immunobiology Program, University of Vermont, Burlington, VT 05405.
Center on Aging and Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030.
J Exp Med. 2016 Oct 17;213(11):2281-2291. doi: 10.1084/jem.20160417. Epub 2016 Sep 26.
IL-6 is known to contribute to the differentiation of CD4 T cells into different subsets of effector T helper cells. Less is known about the potential of IL-6 in regulating CD8 T cell effector function. Here, we identify IL-6 as a master regulator of IL-21 in effector CD8 T cells. IL-6 promotes the differentiation of a subset of naive CD8 T cells that express IL-6R into a unique population of effector CD8 T cells characterized by the production of high levels of IL-21 and low levels of IFN-γ. Similar to CD4 T follicular helper (Tfh) cells, IL-21-producing CD8 T cells generated in the presence of IL-6 directly provide help to B cells to induce isotype switching. CD8 T cell-derived IL-21 contributes to the production of protective virus-specific IgG antibodies during influenza virus infection. Thus, this study reveals the presence of a new mechanism by which IL-6 regulates antibody production during viral infection, and a novel function of effector CD8 T cells in the protection against viruses.
已知白细胞介素-6（IL-6）有助于CD4 T细胞分化为不同亚群的效应性辅助性T细胞。关于IL-6在调节CD8 T细胞效应功能方面的潜力，人们了解得较少。在此，我们确定IL-6是效应性CD8 T细胞中白细胞介素-21（IL-21）的主要调节因子。IL-6促进一部分表达IL-6受体的初始CD8 T细胞分化为独特的效应性CD8 T细胞群体，其特征是产生高水平的IL-21和低水平的干扰素-γ（IFN-γ）。与CD4滤泡辅助性T（Tfh）细胞类似，在IL-6存在的情况下产生的产生IL-21的CD8 T细胞直接为B细胞提供帮助以诱导同种型转换。CD8 T细胞衍生的IL-21在流感病毒感染期间有助于产生保护性病毒特异性IgG抗体。因此，本研究揭示了一种新机制，即IL-6在病毒感染期间调节抗体产生，以及效应性CD8 T细胞在抗病毒保护中的新功能。
