Sarnacki S, Calise D, Brousse N, Cerf-Bensussan N, Révillon Y
Laboratoire de Chirurgie expérimentale, CHU Necker, Paris.
Chirurgie. 1991;117(9):710-6.
In some strain combinations of rats, orthotopic liver transplantation (OLT) permits long-term donor-specific survival of fully allogeneic kidney, heart or skin grafts. The difficulties encountered in the clinical situation to obtain tolerance of small-bowel transplantation (SBT), in spite of massive non-specific immunosuppression, led us to study possible liver-induced tolerance in SBT. Inbred DA (RTIa) and PVG (RT1c) rats were used respectively as donors and recipients and divided in two groups: group 1: SIT alone (n = 6); group 2: combined OLT/SBT (n = 6). SIT was performed 17 days after OLT. No immunosuppressive treatment was given to the recipients. Biopsies of small-bowel grafts were performed in both groups at various times after small bowel engraftment. All animals in group 1 showed evidence of acute rejection of the graft between days 6 and 9 post-graft. The histologic pattern of rejection associated lamina propria (LP) mononuclear cell infiltration, crypt lesions and villous atrophy at the end-point of rejection. In group 2, long-term survival (> 100 days) of small bowel grafts was achieved in five of the six animals in spite of strong mononuclear cell infiltration in the LP, which peaked two months after small bowel grafting but then disappeared partially. This striking mononuclear cell infiltrate contrasted with only minor epithelial damage. These data demonstrate that liver grafting can enhance the survival of a small-bowel graft from the same donor in a rat model. Histological findings show that an intense immunological reaction takes place within liver-induced tolerated small-bowel grafts.
在大鼠的某些品系组合中,原位肝移植(OLT)可使完全同种异体的肾、心脏或皮肤移植物长期存活于供体特异性环境中。尽管采用了大量非特异性免疫抑制措施,但在临床情况下获得小肠移植(SBT)耐受性仍存在困难,这促使我们研究肝脏诱导的SBT耐受性。近交系DA(RTIa)和PVG(RT1c)大鼠分别用作供体和受体,并分为两组:第1组:单独进行SIT(n = 6);第2组:OLT/SBT联合移植(n = 6)。SIT在OLT后17天进行。受体未接受免疫抑制治疗。两组在小肠移植后的不同时间对小肠移植物进行活检。第1组所有动物在移植后第6至9天均出现移植物急性排斥反应的证据。排斥反应的组织学模式表现为固有层(LP)单核细胞浸润、隐窝病变和排斥反应终点时的绒毛萎缩。在第2组中,尽管LP中有强烈的单核细胞浸润,6只动物中有5只实现了小肠移植物的长期存活(> 100天),这种浸润在小肠移植后两个月达到峰值,但随后部分消失。这种显著的单核细胞浸润与轻微的上皮损伤形成对比。这些数据表明,在大鼠模型中,肝脏移植可提高来自同一供体的小肠移植物的存活率。组织学研究结果表明,在肝脏诱导的耐受性小肠移植物中发生了强烈的免疫反应。