Vaccine Induced Activation of T Follicular Helper Cell Subsets

先天免疫和适应性免疫都在接种疫苗后被激活。我们最近证明， 获得性免疫臂（细胞和体液免疫）是由不同类型的骨髓细胞特异性诱导的。 树突状细胞（DC）亚群。特别地，IL-12诱导能够帮助B细胞的CD 4 + T细胞的发育。 IL-21是一种能有效促进B细胞生长、分化和类别转换的细胞因子。 这些CD 4-I-T细胞与T滤泡辅助细胞（Tfh）具有相同的特性，Tfh是最近建立的一种免疫调节细胞。 特化B细胞辅助性CD 4-f T细胞亚群。人Tfh细胞可以在次级淋巴细胞的生发中心中找到。 在淋巴器官和血液中，其特征在于表达趋化因子受体CXCRS和趋化因子受体CXCRs。 IL-21的分泌。因此，Tfh细胞似乎在抗体反应的发展中起着重要作用。 接种疫苗后。然而，关于疫苗如何诱导Tfh应答以及诱导的Tfh应答如何影响免疫应答， 细胞调节抗体反应。我们最近的研究表明，来自人类血液的Tfh细胞由以下组成： 功能不同的子集。本项目的主要假设是Tfh的差异动员 亚群决定了疫苗诱导的体液免疫的质量和数量。特别是，我们假设 阳性疫苗结果与辅助性Tfh细胞的激活有关（即，Tfh 2和Tfhl 7细胞）。在 相反，阴性疫苗结果与辅助性Tfh细胞活化缺陷或抑制性Tfh细胞过度活化有关，即，Tfhl细胞。在这个项目中，我们将建立分子签名， 基线时和流感后激活时的血液Tfh细胞及其功能不同的组分 预防针该项目的最终目标是生成允许对以下内容进行高保真评估的工具： Tfh亚群的体内活化和对疫苗的保护性应答的预测。

Innate and adaptive immunity are both activated upon vaccination. We have recently demonstrated that the two adaptive immune arms (cellular and humoral immunity) are uniquely induced by different types of myeloid dendritic cell (DC) subsets. In particular, IL-12 induces the development of CD4+ T cells capable of helping B cells through the secretion of IL-21, a cytokine that potently promotes B cell growth, differentiation, and classswitching. These CD4-I- T cells share properties with T follicular helper cells (Tfh), a recently established specialized B cell-helper CD4-f T cell subset. Human Tfh cells can be found in the germinal centers of secondary lymphoid organs and in blood, and are characterized by the expression of the chemokine receptor CXCRS and the secretion of IL-21. Thus, Tfh cells appear to playa fundamental role in the developmentof antibody responses ¿ upon vaccination. However, little is known about how vaccines induce Tfh responses and how the induced Tfh cells regulate antibody responses. Our recent studies indicate that Tfh cells from human blood are composed of functionally distinct subsets. The main hypothesis of this project is that the differential mobilization of Tfh subsets dictates the quality and quantity of vaccine-induced humoral immunity. In particular, we hypothesize that a positive vaccine outcome is associated with activation of helper Tfh cells (i.e., Tfh2 and Tfhl7 cells). In contrast, a negative vaccine outcome is associated with either a defect of helper Tfh cell activation or an overactivation of suppressor Tfh cells, i.e., Tfhl cells. In this Project, we will establish the molecular signatures of blood Tfh cells and their functionally different components at baseline, and upon activation following Flu vaccination. The ultimate goal of this Project is to generate tools that will permit high fidelity assessment of in vivo activation of Tfh subsets and prediction of protective responses to vaccines.