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

在同种异体干细胞移植（SCT）中，供体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，并防止移植物排斥反应。然而，供体T细胞也会引发致死性GVHD。在小鼠研究中，我们已经证明CD4+ Th2细胞可以降低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，GVHD大大降低。作为这些结果的翻译，我们已经启动了一项临床试验，评估在异体SCT环境中体外生成的供体Th2细胞。评估Tc2细胞的临床试验也计划用于预防移植排斥（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。

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.