Antibody-mediated rejection (ABMR) is one of the main obstacles to successful transplantation, including ABO blood group-incompatible (ABOi) transplantation. Recently, chimeric antigen receptor regulatory T cells (CAR Tregs) were developed to improve the antigen specificity, viability, and suppressive activity of Tregs. C4d deposition is a marker of ABMR and is also found in most ABOi allograft tissues. Based on these findings, we developed anti-C4d CAR Tregs to suppress ABMR in ABOi allografts. Anti-C4d CAR Tregs prepared by retroviral transduction of CAR into CD62L + CD4 + CD25 + Tregs, expressed Foxp3, CD25, CTLA-4, LAP, and GITR to similar extents as non-transduced Tregs. Anti-C4d CAR Tregs were activated by specific binding to C4d and suppressed in vitro T cell proliferation as well as nontransduced Tregs. Furthermore, adoptive transfer of anti-C4d CAR Tregs significantly prolonged mouse ABOi heart allograft survival (P < 0.05). In conclusion, anti-C4d CAR Tregs are promising therapeutic agents for controlling ABMR in ABOi allografts.

抗体介导的排斥反应 (ABMR) 是成功移植的主要障碍之一，包括 ABO 血型不相容 (ABOi) 移植。最近，开发了嵌合抗原受体调节性 T 细胞 (CAR Tregs) 以提高 Tregs 的抗原特异性、活力和抑制活性。C4d 沉积是 ABMR 的标志，也存在于大多数 ABOi 同种异体移植组织中。基于这些发现，我们开发了抗 C4d CAR Tregs 来抑制 ABOi 同种异体移植物中的 ABMR。通过将 CAR 逆转录病毒转导到 CD62L + CD4 + CD25 + Treg 中制备的抗 C4d CAR Treg，表达 Foxp3、CD25、CTLA-4、LAP 和 GITR 的程度与未转导的 Treg 相似。抗 C4d CAR Tregs 通过与 C4d 的特异性结合而被激活，并抑制体外 T 细胞增殖以及非转导的 Tregs。此外，抗 C4d CAR Tregs 的过继转移显着延长了小鼠 ABOi 心脏同种异体移植物的存活时间（P < 0.05）。总之，抗 C4d CAR Tregs 是用于控制 ABOi 同种异体移植物中 ABMR 的有前途的治疗剂。