Th1/Th2 and Tc1/Tc2 T Cell Subsets in Transplantation Th

移植中的 Th1/Th2 和 Tc1/Tc2 T 细胞亚群

• 批准号: 6758292
• 负责人: DANIEL FOWLER
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6758292
• 关键词: autologous transplantation; bone marrow purging; bone marrow transplantation; cellular immunity; chronic lymphocytic leukemia; clinical research; clinical trials; cytokine; cytolysis; cytotoxic T lymphocyte; graft versus host disease; histocompatibility; homologous transplantation; human subject; human therapy evaluation; laboratory mouse; transplant rejection; transplantation immunology

In allogeneic stem cell transplantation (SCT), donor T cells mediate beneficial immunity such as the graft-versus-leukemia (GVL) and graft-versus-tumor (GVT) effect and prevent graft rejection. However, donor T cells also initiate lethal GVHD. In murine studies, we have shown that CD4+ Th2 cells reduce GVHD. We have also shown that donor CD8+ Tc2 cells can mediate GVL and GVT effects and prevent marrow rejection with greatly reduced GVHD. As a translation of these results, we have initiated a clinical trial evaluating in vitro generated donor Th2 cells in the allogeneic SCT setting. Clinical trials evaluating Tc2 cells are also planned for the purpose of preventing graft rejection in the setting of HLA-disparate transplantation. Ongoing murine studies are evaluating the molecular mechanisms of Th2 and Tc2-mediated immunity in the transplant setting, and in developing approaches to modulate Th1- and Tc1-mediated GVHD. Our lab is additionally evaluating T cell subsets, in particular the Th1 and Tc1 subsets, in the syngeneic setting. These subsets are associated with GVHD in the allogeneic setting, but are likely important anti-tumor mediators in the syngeneic setting. Murine studies are ongoing to evaluate the role of Th1 and Tc1 cells in anti-tumor immunity, particularly in the vaccine setting.

在异基因干细胞移植(SCT)中，供者T细胞介导有益免疫，如移植物抗白血病(GVL)和移植物抗肿瘤(GVT)效应，防止移植物排斥反应。然而，捐赠者的T细胞也会引发致命的移植物抗宿主病。在小鼠的研究中，我们已经证明了CD4+Th2细胞可以降低GVHD。我们还发现，供者CD8+Tc2细胞可以介导GVL和GVT效应，并在显著降低GVHD的情况下防止骨髓排斥反应。作为这些结果的翻译，我们已经启动了一项临床试验，评估在异基因SCT环境中体外产生的供体Th2细胞。评估Tc2细胞的临床试验也计划用于在不同的人类白细胞抗原移植中预防移植物排斥反应。正在进行的小鼠研究正在评估移植环境中Th2和Tc2介导的免疫的分子机制，以及开发调节Th1和Tc1介导的GVHD的方法。 我们的实验室还在评估同基因环境下的T细胞亚群，特别是Th1和Tc1亚群。这些亚群在异基因环境中与GVHD相关，但在同基因环境中可能是重要的抗肿瘤介质。小鼠的研究正在进行中，以评估Th1和Tc1细胞在抗肿瘤免疫中的作用，特别是在疫苗设置中。