Vaccine Induced Activation of T Follicular Helper Cell Subsets

接种疫苗后，先天免疫和获得性免疫都会被激活。我们最近已经证明，这两个 适应性免疫臂(细胞免疫和体液免疫)由不同类型的髓系细胞独一无二地诱导。 树突状细胞(DC)亚群。尤其是IL-12诱导的CD4+T细胞的发育能够帮助B细胞 通过分泌IL-21，一种细胞因子，有效地促进B细胞的生长、分化和分类转换。 这些CD4-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 特化的B细胞辅助性CD4-f T细胞亚群。人TFH细胞可见于继发性卵巢癌的生发中心。 淋巴器官和血液中，其特征是趋化因子受体CXCRS和 IL-21的分泌。因此，TFH细胞似乎在抗体反应的发展中起着基础性作用。 在接种疫苗后。然而，关于疫苗如何诱导转铁蛋白反应以及如何诱导转铁蛋白，人们知之甚少。 细胞调节抗体反应。我们最近的研究表明，人类血液中的TFH细胞由以下成分组成 在功能上不同的子集。该项目的主要假设是TFH的差异性动员 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Tfh细胞(即Tfh2和Tfhl7细胞)的激活有关。在……里面 相比之下，阴性疫苗结果与辅助性Tfh细胞激活缺陷或抑制性Tfh细胞(即Tfhl细胞)过度激活有关。在这个项目中，我们将建立分子签名 血液TFH细胞及其功能不同的成分在基线和流感后激活时 接种疫苗。该项目的最终目标是生成工具，使高保真评估成为可能 TFH亚群的活体激活和疫苗保护性反应的预测。

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.