Experimental study on peripheral nerve xenograft by induction of immuno-tolerance

抗cd4治疗已被证明可以延长同种异体皮肤移植和心脏移植的存活时间。抗cd4和抗cd8单克隆抗体延长大鼠异种心脏移植存活时间，融合蛋白CTLA4Ig阻断T细胞依赖性抗体的产生，抑制同种异体细胞系再刺激活化T细胞的增殖。我们在手术显微镜下采用显微外科技术将长度为10mm的Lewis大鼠腓肠神经移植到小鼠（BALB/c）坐骨神经缺损3mm处。实验动物分为3组：1组（对照组）；未治疗组为第二组；a组小鼠在移植后2天及移植前立即腹腔注射抗cd4 （125 μg/只），在移植后1天及移植后3天腹腔注射CTLA4Ig （25μg/只）。术后8周取移植神经标本进行组织学检查。术后8周，三组后肢运动功能恢复情况无明显差异。组织学检查结果如下：1组胶原纤维形成明显，再生髓鞘轴突在异种移植物中仅呈散在状，轴突直径小，髓鞘薄。2、3组则相反，在移植物神经中弥漫性观察到许多有髓鞘的轴突。与1组相比，再生的轴突直径更大，髓鞘更厚。本研究表明，短期少量给药抗cd4或CTLA4Ig可使大鼠和小鼠周围神经异种移植的轴突再生

Anti-CD4 treatment has been shown to prolong survival of skin allografts as well as cardiac allografts. Anti-CD4 and anti-CD8 monoclonal antibodies prolonged concordant rat-to-mouse cardiac xenograft survival The fusion protein, CTLA4Ig, blocks T-cell-dependent antibody production and inhibits the proliferation of activated T cells restimulated with allogeneic cell linesWe transplanted Lewis rat sural nerve of 10mm length to the defect of mouse (BALB/c) sciatic nerve of 3mm using microsurgical technique under operating microscope. The experimental animals were divided into the following three groups : Group 1 (control) ; no treatment, Group 2 ; anti-CD4 (125/μg mouse) was given intraperitoneally on 2 days and immediately before transplantaticn, Group a CTLA4Ig (25μg/mouse) was given intraperitoneally just after transplantaticn and on 1 day and 3 days after transplantation. We examined the motor function recovery by Waking tract analysis and the specimen of the grafted nerve was taken at 8 weeks after transplantation for histological examinationThe walking tract test showed no evident differences in recovery of hindlimb motor function for 8 weeks after transplantation between three groups. The histological examination revealed the following results : In Group 1, there was remarkable formation of collagen fibers and the regenerated myelinated axons were only scattered in the xenograft and the diameter of the axon was small and the myelin sheath was thin. In Group 2, 3, on the contrary, many myelinated axons were observed diffusely in the grafted nerve. And the diameter of the regenerated axons was larger and the myelin sheath was thicker than Group 1From this study we conclude that short-term and small amount of administration of anti-CD4 or CTLA4Ig enables the axonal regeneration through peripheral nerve xenograft between rat and mouse