Shen Z, Kline G, Mohiuddin M, DiSesa V J
Division of Cardiothoracic Surgery, Medical College of Pennsylvania, Philadelphia 19129.
J Thorac Cardiovasc Surg. 1994 Jun;107(6):1472-5.
Control of cardiac transplant rejection without toxic immunosuppressive drugs remains an unreached goal. Our laboratory and others have shown that intrathymic inoculation of donor-specific allogeneic spleen cells can produce tolerance to a subsequent cardiac allograft. The present experiments were designed to investigate whether the degree of donor-recipient histoincompatibility influenced the efficacy of this technique. Four congeneic strains of rats with different degrees of histoincompatibility were studied. Heterotopic cardiac transplantation was done with the following congeneic strain combinations: DA donor into PVG recipient (full major histocompatibility complex and nonmajor histocompatibility complex incompatibility); PVG.RT1a donor into PVG recipient (full major histocompatibility complex incompatibility); PVG.RT1a donor into PVG.R1 recipient (partial major histocompatibility complex incompatibility). Prospective graft recipients underwent intraperitoneal injection of 1 ml antilymphocyte serum and intrathymic injection of 5 x 10(7) prospective donor spleen cells. Three weeks later, heterotopic cardiac transplantation was done with a heart from a donor of the same strain as that used to obtain splenocytes for intrathymic injection. Prolongation of graft survival was observed in pretreated recipients in all strain combinations but was greatest in recipients that differed from donors at fewer histocompatibility loci. Complete graft tolerance was not seen in strain combinations that included nonmajor histocompatibility complex incompatibilities. DA heart survival in PVG recipients was 50.6 days (p < 0.04 versus controls); PVG.RT1a graft survival in PVG hosts was 165.8 days (p < 0.02 versus control) and in PVG.R1 recipients 163.8 days (p < 0.02 versus controls) with four of five grafts in each group surviving indefinitely (more than 200 days).
在不使用毒性免疫抑制药物的情况下控制心脏移植排斥反应仍是一个尚未实现的目标。我们实验室以及其他一些机构已经表明，胸腺内接种供体特异性同种异体脾细胞可诱导对随后心脏同种异体移植物的耐受性。本实验旨在研究供体 - 受体组织相容性不相容程度是否会影响该技术的疗效。我们研究了四种具有不同程度组织相容性不相容的同基因大鼠品系。采用以下同基因品系组合进行异位心脏移植：DA供体到PVG受体（完全主要组织相容性复合体和非主要组织相容性复合体不相容）；PVG.RT1a供体到PVG受体（完全主要组织相容性复合体不相容）；PVG.RT1a供体到PVG.R1受体（部分主要组织相容性复合体不相容）。预期的移植物受体接受腹腔注射1毫升抗淋巴细胞血清，并在胸腺内注射5×10⁷预期供体脾细胞。三周后，用与用于胸腺内注射获取脾细胞的供体相同品系的心脏进行异位心脏移植。在所有品系组合中，预处理受体的移植物存活时间均有延长，但在组织相容性位点差异较少的受体中延长最为显著。在包括非主要组织相容性复合体不相容的品系组合中未观察到完全的移植物耐受性。PVG受体中DA心脏的存活时间为50.6天（与对照组相比，p<0.04）；PVG宿主中PVG.RT1a移植物的存活时间为165.8天（与对照组相比，p<0.02），在PVG.R1受体中为163.8天（与对照组相比，p<0.02），每组五只移植物中有四只无限期存活（超过200天）。
