Novel pathways in T lymphocyte differentiation and function

T 淋巴细胞分化和功能的新途径

• 批准号: RGPIN-2015-05491
• 负责人: King, Irah
• 金额: $ 2.11万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=590462
• 关键词: Novel; pathways; lymphocyte; differentiation; function

The ability to generate high-affinity antibodies to diverse infectious agents (i.e. humoral immunity) is a fundamental property of the vertebrate immune system and ensures host survival. The humoral immune response requires highly coordinated interactions between B lymphocytes (which possess antibody-producing potential) and “helper” T cells. These interactions are mediated by a subset of helper T cells termed T follicular helper (Tfh) cells that provide direct help to B cells through provision of membrane-bound co-stimulatory molecules and secretion of polarizing cytokines. We have previously shown that Tfh cells provide critical sources of interleukin (IL)-4 and IL-21 required for the generation of humoral immune responses in the context of immunization (King et al, Nature Immunology, 2012) and parasitic helminth infection (King and Mohrs, Journal of Experimental Medicine, 2009). This proposal builds on these findings to identify previously undescribed molecules and signaling pathways that specifically control T cell differentiation and function.

产生针对不同感染因子的高亲和力抗体（即体液免疫）的能力是脊椎动物免疫系统的基本特性，并确保宿主存活。体液免疫反应需要B淋巴细胞（具有抗体产生潜力）和“辅助”T细胞之间高度协调的相互作用。这些相互作用由称为T滤泡辅助（Tfh）细胞的辅助性T细胞亚群介导，所述辅助性T细胞通过提供膜结合共刺激分子和分泌极化细胞因子而向B细胞提供直接帮助。我们先前已经表明，Tfh细胞提供了在免疫（King等，Nature Immunology，2012）和寄生蠕虫感染（King和Mohrs，Journal of Experimental Medicine，2009）的背景下产生体液免疫应答所需的白介素（IL）-4和IL-21的关键来源。该提案建立在这些发现的基础上，以确定以前未描述的分子和信号通路，这些分子和信号通路特异性地控制T细胞分化和功能。