Analysis of Rejection Mechanism and Indutcion of Unresponsiveness in Organ Transplantation

众所周知，主要组织相容性复合体（MHC）对移植物是否被接受或排斥起着重要作用。本研究采用同种异体移植大鼠肾脏，探讨诱导免疫无反应的最有效方法。排斥模型以to （RT1^u）、LEW （RT1^l）、F344 （RT1^<lv>）大鼠为供体，WKAH （RT1^k）大鼠为受体。所有移植物均在16 d内发生排异反应。(1)抗ia单克隆抗体：供体（F344）肾移植前灌注1mg抗F344- ia抗体（4B4），将灌注后的移植物移植至WKAH大鼠（灌注组）。另一实验，我们在灌注肾移植后给WKAH大鼠静脉注射抗受体- ia抗体（1E4）（灌注+iv组）。两组患者的平均生存时间均显著延长。然而，没有显著的长期幸存者。(2)供体脾细胞预免疫：受体大鼠（WKAH）在移植前1周用5 × 10^7供体脾细胞预免疫。8只预免疫大鼠中有6只存活超过192天。(3)短期给药15-脱氧桔果苷（DSG）：将大鼠肾移植至WKAH大鼠。DSG组从术后第4天开始，连续4天肌注DSG 5mg/kg/d。DSG短期给药（仅4天）诱导同种异体移植物无限期存活。长期存活机制分析从TO到预免疫的WKAH大鼠进行同种异体肾移植后，受体血清在移植后2周内非特异性抑制MLR，但在4周后无抑制作用。ox8阳性细胞持续抑制供体型细胞的MLR。在DSG组，WKAH大鼠接受TO皮肤移植，但排斥其他品系的皮肤移植。这些数据表明，DSG诱导的无反应性是供体特异性的。少

It is well known that the major histocompatibility complex (MHC) plays an important role as to whether a graft is accepted or rejected. In the present study, rat renal allografting was performed to investigate the most effective methods that induce immunological unresponsiveness.1. Rejection modelTO (RT1^u), LEW (RT1^l), F344 (RT1^<lv>) rats were used as donors, and WKAH (RT1^k) rats as recipients. All these grafts were rejected within 16 days.2. Experiments for prolongation of allograft survival(1) Anti-Ia monoclonal antibody : The donor (F344) kidney was perfused with 1mg of anti-F344-Ia antibody (4B4) before transplantation, then the perfused graft was transplanted to WKAH rats (perfusion group). To make another experiment, we administered anti-recipient-Ia antibody (1E4) intravenously to WKAH rat after the perfused kidney was transplanted (perfusion^+iv group). Mean survival time of these 2 group prolonged significantly. However, there was no significant long suvivor.(2) Preimmunza … More tion with donor strain spleen cells : The recipient rat (WKAH) was preimmunized with 5x10^7 donor strain (TO) spleen cells 1 week prior to transplantation. Six of 8 preimmunized rat survived more than 192 days.(3) Short term administration of 15-deoxyspergualin (DSG) : TO rat kidney was transplanted to WKAH rat. In DSG group, 5mg/kg/day DSG was administered intramuscularily for 4 days from the 4th postoperative day. The short term administration (only 4 days) of DSG induced indefinite allograft survival.3. Analysis of mechanisms of long term survivingAfter renal allografting was performed from TO to preimmunized WKAH rats, recipients sera suppressed MLR nonspecifically for 2 weeks after grafting, but had no suppressive effect after 4 weeks. OX 8 positive cells continuously suppressed MLR specifically in donor type cells. In the DSG group, WKAH rat accepted TO skin graft, but rejected the skin grafts from other strain. These data indicated that the unresponsiveness induced by DSG was donor specific. Less