Compartimentalization, maintenance and reactivation of human bone marrow resident and blood circulating memory T lymphocytes

人骨髓驻留和血液循环记忆 T 淋巴细胞的区室化、维持和重新激活

• 批准号: 389687267
• 负责人: Dr. Jun Dong
• 金额: --
• 依托单位: Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/389687267?language=en
• 关键词: Compartimentalization; maintenance; reactivation; human; bone

The paradigm that memory T lymphocytes are continuously circulating through the body in search of their cognate antigen has recently been challenged by the discovery of memory T cells residing in a variety of tissues, including the bone marrow. However, the division of labor and lifestyle of resident versus circulating memory T cells remain enigmatic. We have obtained initial evidence that memory T cells residing in the human bone marrow are neither circulating nor activated. For example, despite expressing CD69, proliferation and global gene expression analyses have characterized these cells as resting cells. In addition, CD4+ memory T cells specific for systemic viral childhood antigens, like measles, have been found in the bone marrow of elderly humans, but not among circulating memory T cells. From these results, we hypothesize that bone marrow memory T cells are resident, resting and maintain long-term memory to systemic antigens.In the proposed project, we will test and extend this hypothesis. Specifically, we will address how memory T cells are compartmentalized, maintained, and reactivated upon systemic re-challenges. This approach will significantly contribute to our understanding of human T cell memory, which provides the rationale for modulation of immunity by vaccines and immunotherapies.

记忆T淋巴细胞在体内持续循环寻找同源抗原的模式最近受到了挑战，因为发现了驻留在包括骨髓在内的各种组织中的记忆T细胞。然而，居民和循环记忆T细胞的分工和生活方式仍然是个谜。我们已经获得了初步证据，即驻留在人类骨髓中的记忆T细胞既不循环也不激活。例如，尽管表达CD69，但增殖和全球基因表达分析已将这些细胞定性为静息细胞。此外，在老年人的骨髓中发现了针对系统性病毒童年抗原(如麻疹)的CD4+记忆T细胞，但在循环中的记忆T细胞中没有发现。根据这些结果，我们假设骨髓记忆T细胞是驻留的，休息并维持对系统抗体的长期记忆。在拟议的项目中，我们将测试和扩展这一假设。具体地说，我们将解决记忆T细胞是如何被区分、维护和在系统性重新挑战时重新激活的。这种方法将大大有助于我们对人类T细胞记忆的理解，这为疫苗和免疫疗法调节免疫提供了理论基础。