The role of ICOS for T follicular helper responses

T滤泡辅助细胞（TFH）的特殊亚群对体液免疫反应至关重要。没有TFH细胞，就不会产生高亲和力抗体或长寿命浆细胞。因此，TFH细胞也是自身免疫性疾病治疗干预的一个有希望的靶点。通过诱导共刺激物ICOS，我们已经确定了TFH产生和/或维持的关键调节因子。借助基于抗原特异性T细胞和B细胞过继转移到免疫活性小鼠体内的小鼠体内T/B合作系统，我们希望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、免疫组织学和双光子体内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细胞和B细胞的命运。我们特别感兴趣的是生发中心内T/B合作的动态。在第二部分中，我们希望在ICOS体内阻断后重新分离抗原特异性TFH细胞并分析其转录组。使用逆转录病毒表达系统，我们将测试ICOS调节基因与TFH发育和功能的功能相关性。

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.