Noble A, Zhao J
MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK.
Clin Exp Allergy. 2016 Aug;46(8):1075-82. doi: 10.1111/cea.12750. Epub 2016 Jun 6.
Th2 cells have long been considered responsible for the switching of B cells to production of IgE during cognate interaction, primarily due to their expression of CD40L and secretion of IL-4. This concept has been challenged by the more recent definition of follicular helper T cells (Tfh) as the key T cell subset in B cell isotype switching, due to their physical location at the boundary of T cell:B cell areas in lymphoid follicles and ability to express IL-4 and CD40L.
To determine whether Tfh cells are responsible for IgE responses to Der p 1 allergen after house dust mite (HDM)-induced allergic sensitization.
Mice deficient in Tfh cells were sensitized to HDM and Der p 1-specific IgE measured by ELISA.
Mice with a mutation in T cell-expressed IL-6R were unable to expand Tfh populations after HDM sensitization, and their anti-Der p 1 IgE, IgG1 and total IgE responses were reduced by 80-90% compared with wild-type mice. These animals displayed unaltered lung Th2 and eosinophilic responses after intranasal HDM challenge and normal IL-4 production, but B cell infiltration of the airways was abrogated.
Our data indicate that Tfh cells are largely responsible for switching B cells to IgE synthesis, most likely via an IgG1(+) intermediate. However, Th2 cells are the major source of IL-4 during HDM sensitization and this might contribute to IgE synthesis at a stage distal to Tfh-mediated isotype switching. The IL-6/follicular helper T cell pathway is a potential therapeutic target in allergic disease.
长期以来，Th2细胞一直被认为在同源相互作用过程中负责促使B细胞转换为产生IgE，主要是因为它们表达CD40L并分泌IL-4。然而，滤泡辅助性T细胞（Tfh）作为B细胞同种型转换中的关键T细胞亚群的最新定义对这一概念提出了挑战，这是由于它们位于淋巴滤泡中T细胞与B细胞区域的边界处，并且能够表达IL-4和CD40L。
确定Tfh细胞是否在屋尘螨（HDM）诱导的过敏致敏后对Der p 1变应原的IgE反应中起作用。
使缺乏Tfh细胞的小鼠对HDM致敏，并通过ELISA检测Der p 1特异性IgE。
T细胞表达的IL-6R发生突变的小鼠在HDM致敏后无法扩增Tfh群体，与野生型小鼠相比，它们的抗Der p 1 IgE、IgG1和总IgE反应降低了80-90%。这些动物在经鼻HDM攻击后肺Th2和嗜酸性粒细胞反应未改变，IL-4产生正常，但气道的B细胞浸润被消除。
我们的数据表明，Tfh细胞在很大程度上负责促使B细胞转换为IgE合成，最有可能通过IgG1(+)中间体。然而，Th2细胞是HDM致敏期间IL-4的主要来源，这可能在Tfh介导的同种型转换的远端阶段促进IgE合成。IL-6/滤泡辅助性T细胞途径是过敏性疾病的一个潜在治疗靶点。
