Graft-versus-host disease (GVHD) and transplant rejection as a result of host-versus-graft (HVG) response have remained two major complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). When donors are partially HLA-mismatched unrelated or haploidentical related, their severity correlates with the degree of HLA disparity. Specific elimination of alloreactive donor or recipient T cells targeting the mismatched HLA products could markedly alleviate both complications while only minimally affecting graft-versus-tumor (GVT) response or engraftment.

To redirect human CD8 T cells against alloreactive CD8 T cells we electroporate these cells with in-vitro-transcribed mRNA encoding MHC-I heavy chains fused with the signaling portion of CD3ζ. Here we show that peripheral blood human CD8 T cells expressing H-2K^b/CD3ζ or H-2K^d/CD3ζ respond to anti-MHC-I stimuli in a strictly specific manner. This study paves the way for further advancing this approach as a means to dampen GVHD and HVG that are caused by HLA disparity in allo-HSCT.

异体造血干细胞移植（allo-HSCT）仍然是移植物抗宿主病（GVHD）和宿主抗移植物（HVG）反应导致的移植排斥的两个主要并发症。当供体部分与HLA不匹配或单亲相关时，其严重程度与HLA差异程度相关。靶向消除不匹配的HLA产物的同种反应性供体或受体T细胞的特异性消除可以显着减轻两种并发症的发生，而对移植物抗肿瘤（GVT）反应或移植的影响却很小。

为了使人CD8 T细胞针对同种异体反应性CD8 T细胞重定向，我们用体外转录的编码与CD3ζ信号传导部分融合的MHC-1重链的mRNA电穿孔这些细胞。在这里，我们显示表达H-2K ^b /CD3ζ或H-2K ^d /CD3ζ的外周血人CD8 T细胞以严格特异性的方式响应抗MHC-1刺激。这项研究为进一步推进这种方法铺平了道路，这种方法可以缓解由异体HSCT中HLA差异引起的GVHD和HVG。