CD62L-记忆T淋巴细胞在异基因骨髓移植小鼠体内作用机制的研究

Bone marrow transplantation is one of the most effective clinical treatments for benign or malignant diseases of blood system. A major challenge in allogeneic hematopoietic cell transplantation is how to transfer T cell immunity without causing graft-versus-host disease (GVHD). CD62L- memory T cells are a cell subset that can potentially address this challenge because they do not induce GVHD. In our previous study, we investigated how CD62L- memory T cells from contributed to phenotypic and functional T cell reconstitution post allogeneic stem cell transplantation. Upon transfer to allogeneic recipients, CD62L- memory T cells were activated and expressed multiple cytokines and cytotoxic molecules. CD62L- memory T cells were able to deplete host radioresistant T cells and facilitate hematopoietic cell engraftment, resulting in enhanced de novo T cell regeneration from hematopoietic stem cells. Enhanced functional immune reconstitution was demonstrated in CD62L- memory T cell recipients using a tumor and an influenza virus challenge model. At present, the mechanisms about how to regulate immune functions in recipients by CD62L- memory T cells are not clear. Basing on all these previous research, our project mainly focuses on investigating the mechanisms about how CD62L- memory T cells to separate graft-versus-tumor (GVT) from GVHD in mice after allogenieic stem cell transplantation. This study will further highlight the pathogenesis of GVHD and the unique characteristics of CD62L- memory T cells and their potential applications in clinical hematopoietic cell transplantation.

骨髓移植是临床治疗血液系统良恶性疾病最有效的方法之一，如何快速重建移植术后病人的免疫功能且预防移植物抗宿主病的发生是目前研究的热点。本研究前期工作表明，在小鼠骨髓移植后CD62L-记忆T淋巴细胞可促进造血干细胞的植入和血细胞的生成、为受体鼠提供抗感染和抗肿瘤等免疫保护且又不引起移植物抗宿主病，由此提示该细胞的应用将为临床骨髓移植病人术后免疫功能的快速重建和感染、肿瘤复发等严重并发症的预防提供一条有效的治疗途径。目前，对于CD62L-记忆T淋巴细胞如何在受体内发挥和调节自身免疫功能的机制还不清楚。本研究以小鼠同种异体骨髓移植模型为基础，拟从分子、细胞和个体水平研究CD62L-记忆T淋巴细胞在体内外活化、增殖、凋亡及克隆无能等免疫耐受的机制，阐明其在机体内调节自身免疫应答的作用机理，研究结果将为探讨移植物抗宿主病的发病机制和CD62L-记忆T淋巴细胞在临床的应用提供有力的理论和实验依据。