The role of ICOS for T follicular helper responses

ICOS 在滤泡辅助反应中的作用

• 批准号: 194668741
• 负责人: Professor Dr. Andreas Hutloff
• 金额: --
• 依托单位: Institut für Immunologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/194668741?language=en
• 关键词: role; ICOS; follicular; helper; responses

The specialised subpopulation of T follicular helper cells (TFH) is of central importance for the humoral immune response. Without TFH cells no high affinity antibodies or long-lived plasma cells are generated. Therefore, TFH cells are also a promising target for therapeutic intervention in autoimmune diseases. With the inducible costimulator ICOS we have identified a key regulator of TFH generation and/or maintenance. With the help of a murine in vivo T/B cooperation system which is based on the adoptive transfer of antigen-specific T and B cells into immunocompetent mice we want to investigate the underlying molecular mechanisms. In a first part of the project we will use flow cytometry, immunohistology, and two-photon in vivo imaging to analyse how missing or interrupted ICOS costimulation affects the fate of antigen-specific T and B cells. In particular we are interested in the dynamics of T/B cooperation within the germinal centre. In a second part we want to re-isolate antigen-specific TFH cells after ICOS in vivo blockade and analyse their transcriptome. Using a retroviral expression system we will test the functional relevance of ICOS regulated genes for TFH development and function.

T滤泡辅助细胞(TFH)的特殊亚群对于体液免疫反应具有重要意义。如果没有TFH细胞，就不会产生高亲和力抗体或长寿命的浆细胞。因此，TFH细胞也是自身免疫性疾病治疗干预的一个有前途的靶点。通过可诱导的共刺激分子ICOS，我们已经确定了TFH产生和/或维持的关键调节因子。通过将抗原特异性T、B细胞过继转移到具有免疫功能的小鼠体内的T/B协同系统，我们想要研究其潜在的分子机制。在项目的第一部分，我们将使用流式细胞术、免疫组织学和体内双光子成像来分析缺失或中断的ICOS共刺激如何影响抗原特异性T和B细胞的命运。我们尤其感兴趣的是生殖器中心内T/B合作的动态。在第二部分中，我们想要在ICOS体内阻断后重新分离抗原特异性的TFH细胞并分析它们的转录组。利用逆转录病毒表达系统，我们将测试ICOS调控基因与TFH发育和功能的功能相关性。