Pearson T C, Alexander D Z, Winn K J, Linsley P S, Lowry R P, Larsen C P
Department of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322.
Transplantation. 1994 Jun 27;57(12):1701-6.
The rejection of the transplanted allograft is dependent on T cell activation, which requires T cell receptor engagement by antigen and costimulatory signals delivered by T cell surface molecules such as CD28. CTLA4-Ig is a fusion protein that has previously been shown to block the CD28-mediated costimulatory signal and inhibit immune responses in vitro and in vivo. In this report we show that treatment of the C3H/He recipient of a BALB/c vascularized cardiac allograft with a 12-day course of CTLA4-Ig produced indefinite graft survival (> 100 days) in the majority of recipients. In addition, these recipients demonstrated donor-specific transplantation tolerance when tested with donor-specific (BALB/c) and third-party (C57BL/10) skin grafts. These results demonstrate that CTLA4-Ig can induce transplantation tolerance in the adult murine cardiac allograft model.
移植同种异体移植物的排斥反应取决于T细胞活化，这需要抗原与T细胞受体结合以及T细胞表面分子（如CD28）传递的共刺激信号。CTLA4-Ig是一种融合蛋白，先前已证明它能阻断CD28介导的共刺激信号，并在体内外抑制免疫反应。在本报告中，我们表明，用CTLA4-Ig进行为期12天的治疗，可使接受BALB/c血管化心脏同种异体移植的C3H/He受体在大多数受体中实现无限期的移植物存活（>100天）。此外，当用供体特异性（BALB/c）和第三方（C57BL/10）皮肤移植物进行测试时，这些受体表现出供体特异性移植耐受。这些结果表明，CTLA4-Ig可在成年小鼠心脏同种异体移植模型中诱导移植耐受。
