Th1/Th2 & Tc1/Tc2 T Cell Subsets in Transplantation Ther

Th1/Th2

• 批准号: 6558714
• 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/6558714
• 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 mismatched transplantation) and in the setting of tumor relapse post-transplant. Ongoing murine studies are evaluating the molecular mechanisms of Th2 and Tc2-mediated immunity in the transplant setting. 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.

在同种异体干细胞移植 (SCT) 中，供体 T 细胞介导有益免疫，例如移植物抗白血病 (GVL) 和移植物抗肿瘤 (GVT) 效应，并防止移植物排斥。然而，供体 T 细胞也会引发致命的 GVHD。在小鼠研究中，我们发现 CD4+ Th2 细胞可降低 GVHD。我们还表明，供体 CD8+ Tc2 细胞可以介导 GVL 和 GVT 效应并防止骨髓排斥，同时大大降低 GVHD。作为这些结果的转化，我们启动了一项临床试验，评估同种异体 SCT 环境中体外生成的供体 Th2 细胞。还计划评估 Tc2 细胞的临床试验，以防止移植物排斥（在不匹配移植的情况下）和移植后肿瘤复发的情况。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。 我们的实验室还在同基因环境中另外评估 T 细胞亚群，特别是 Th1 和 Tc1 亚群。这些子集在同种异体环境中与 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，特别是在疫苗环境中。