Human antigen-specific T cell responses in viral control and immunopathology

我的小组的主要目标是研究抗原特异性细胞毒性T细胞（CTL）的功能方面，重点是影响CTL控制病毒感染和癌症进展的因素。虽然在人类感染期间，强大和适当的T细胞反应通常对宿主有益，但弱或不适当的反应可能无效甚至产生有害影响。在过去的二十年里，我们一直致力于了解T细胞在许多不同的病毒感染和癌症中有效控制病毒所需的关键因素。为此，我们建立了从组织和血液中分离的抗原特异性T细胞的离体和体外T细胞功能评估平台。通过将这些功能数据与多组学单细胞和T细胞受体（TCR）库分析联系起来，我们已经确定了增强和控制免疫反应的潜在靶点和途径，作为改善包括SARS-CoV-2病毒感染在内的几种重要人类疾病的结果的一种方式。在本提案中，我们将解决病毒感染和疫苗接种后CTL记忆诱导，中枢记忆建立和维持的基本问题，特别关注以SARS-CoV-2为模型系统的组织驻留记忆细胞。我们的目标是建立CTL功能与有效的病毒控制和受影响器官潜在的有害免疫病理的相关性。通过对组织免疫学的研究，我们将为改进疫苗设计和病毒感染的治疗方法提供科学依据和工具。

The main objective of my group is to investigate the functional aspects of antigen specific cytotoxic T cells (CTL) with a focus on the factors affecting CTL in controlling virus infection and cancer progression.While a robust and appropriate T cell response is typically beneficial to the host during human infections, a weak or inappropriate response can be ineffective or even have a detrimental effect. Over the past two decades, our efforts have been on understanding the key factors required for efficient viral control by T cells in a number of different viral infections and cancer. To do this, we have established an ex-vivo and in-vitro T cell functional evaluation platforms for antigen-specific T cells isolated from tissue and blood. By linking these functional data with multi-omic single cell and T cell receptor (TCR) repertoire analysis, we have identified potential targets and pathways to augment and control the immune response as a way of improving the outcome of several important human diseases including SARS-CoV-2 virus infection. In this proposal, we will address fundamental questions in CTL memory induction, central memory establishment and maintenance following virus infection and vaccination, with a particular focus on tissue-resident memory cells using SARS-CoV-2 as the model system. We aim to establish CTL functional relevance to efficient viral control and potential detrimental immunopathology in affected organs. By studying the immunology of tissues, we will provide scientific evidence and tools for improved vaccine design and therapeutic approaches for virus infections.