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

在异基因干细胞移植（SCT）中，供体T细胞介导有益的免疫，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细胞也引发致死性GVHD。在小鼠研究中，我们已经表明，CD4+ Th2细胞减少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，大大减少GVHD。作为这些结果的翻译，我们已经开始了一项临床试验，评估在同种异体SCT设置在体外产生的供体Th2细胞。还计划进行评估Tc2细胞的临床试验，以预防HLA不同移植中的移植物排斥反应。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。 我们的实验室还评估了T细胞亚群，特别是Th1和Tc1亚群，在同源设置。这些亚群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，特别是在疫苗背景下。

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.