Scientific research of transplantation tolerance targeting CD26/caveolin-1 costimulation pathway

在我们的研究中，我们在体外实验中证明，含有小窝蛋白-1 N末端结构域的可溶性Fc融合蛋白(Cav-Ig)阻断CD26介导的T细胞共刺激作用，不仅降低了对Recall抗原的初级和次级增殖反应，也降低了对无关同种异体抗原呈递细胞的初级和次级增殖反应。为了将体外发现扩展到体内系统，我们在异种GVHD(XGVHD)小鼠模型中检测了CD26依赖的器官损伤。注射人源化抗人CD26单抗(MAb)可在不损失人T细胞植入的情况下，降低HU-PBL-NOG小鼠的移植物抗宿主病(XGVHD)严重程度和延长存活时间，而增加CTLA4-Ig剂量则可减少人淋巴细胞的植入。重要的是，抗CD26单抗治疗保留了移植物抗白血病的作用。总之，我们的发现表明CD26在GVHD的调节中发挥作用，并指出CD26是治疗该疾病的新靶点。

In our research, we demonstrated in in vitro experiments that blockade of CD26-mediated T cell costimulation by soluble Fc fusion proteins containing the N-terminal domain of caveolin-1 (Cav-Ig) diminished primary and secondary proliferative responses not only to recall antigen, but also to unrelated allogeneic antigen-presenting cell. To expand the in vitro findings to an in vivo system, we examined CD26-dependent organ injury in a xenogeneic GVHD (xGVHD) murine model. Administration of humanized anti-human CD26 monoclonal antibody (mAb) decreased xGVHD severity and prolonged survival in hu-PBL-NOG mice without loss of engraftment of human T cells, while increasing doses of CTLA4-Ig diminished engraftment of human lymphocytes. Importantly, anti-CD26 mAb treatment preserved the graft-versus-leukemia effects. Altogether, our findings indicate a role for CD26 in the regulation of GVHD and point to CD26 as a novel target for therapeutic intervention in this disease.