Shen Z, Mohiuddin M, Yokoyama H, Reiss G R, DiSesa V J
Department of Cardiothoracic Surgery, Medical College of Pennsylvania, Philadelphia 19129, USA.
J Thorac Cardiovasc Surg. 1996 Nov;112(5):1315-8. doi: 10.1016/S0022-5223(96)70146-0.
Indefinite donor-specific tolerance to a cardiac allograft can be induced through pretransplantation intrathymic injection of donor spleen cells and a single intraperitoneal injection of antilymphocyte serum. This study was designed to determine whether this phenomenon was reproducible with grafts differing in either class I major histocompatibility complex only or class II MHC only. Donors of cells and hearts in all experiments were RP rats. Class I MHC disparate grafts were performed by placing an RP heart into a Lewis recipient, and class II disparate grafts were performed with RP donors and Wistar Furth recipients. Lewis (n = 10) and Wistar Furth (n = 10) recipients underwent intraperitoneal injection of 1 ml antilympocyte serum and intrathymic injection of 5 x 10(7) RP spleen cells. Three weeks later, heterotopic cardiac transplantation was done with a heart from an RP rat. Control rats had no pretreatment or received antilympocyte serum alone. Without pretreatment, RP hearts survived 7 to 9 days (mean 8 days) in Lewis recipients (n = 5) and 9 to 14 days (mean 12 days) in Wistar Furth recipients (n = 5). Antilymphocyte serum alone produced slight prolongation of graft survival. Lewis rats pretreated with class I disparate RP splenocytes and antilympocyte serum had graft survivals of 8 to 27 days (mean 14 days), not significantly different from the results with antilympocyte serum alone. Class II disparate RP grafts placed in pretreated Wistar Furth rats had significant prolongation of graft survival, with four of five grafts surviving longer than 60 days (p < 0.01 vs antilympocyte serum alone). These results suggest that a disparity at the class II locus of the major histocompatibility complex is critical for the induction of cardiac allograft tolerance after intrathymic inoculation of allogeneic cells.
通过移植前胸腺内注射供体脾细胞和单次腹腔内注射抗淋巴细胞血清，可诱导对心脏同种异体移植物产生不确定的供体特异性耐受。本研究旨在确定这种现象在仅I类主要组织相容性复合体不同或仅II类MHC不同的移植物中是否可重现。所有实验中的细胞和心脏供体均为RP大鼠。I类MHC不相合移植物是将RP心脏植入Lewis受体，II类不相合移植物是用RP供体和Wistar Furth受体进行。Lewis（n = 10）和Wistar Furth（n = 10）受体接受腹腔内注射1 ml抗淋巴细胞血清和胸腺内注射5×10⁷个RP脾细胞。三周后，用来自RP大鼠的心脏进行异位心脏移植。对照大鼠未进行预处理或仅接受抗淋巴细胞血清。未经预处理时，RP心脏在Lewis受体（n = 5）中存活7至9天（平均8天），在Wistar Furth受体（n = 5）中存活9至14天（平均12天）。单独使用抗淋巴细胞血清可使移植物存活时间略有延长。用I类不相合的RP脾细胞和抗淋巴细胞血清预处理的Lewis大鼠，其移植物存活时间为8至27天（平均14天），与单独使用抗淋巴细胞血清的结果无显著差异。置于预处理的Wistar Furth大鼠中的II类不相合RP移植物，其移植物存活时间显著延长，五只移植物中有四只存活超过60天（与单独使用抗淋巴细胞血清相比，p < 0.０1）。这些结果表明，主要组织相容性复合体II类位点的差异对于胸腺内接种异基因细胞后诱导心脏同种异体移植物耐受至关重要。
