Lin Y, Soares M P, Sato K, Takigami K, Csizmadia E, Smith N, Bach F H
Immunobiology Research Center, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
J Immunol. 1999 Sep 1;163(5):2850-7.
Hamster hearts transplanted into transiently complement-depleted and continuously cyclosporin A (CyA)-immunosuppressed rats survive long-term despite deposition of anti-donor IgM Abs and complement on the graft vascular endothelium. This phenomenon is referred to as "accommodation." The hypothesis tested here is that accommodated xenografts are resistant to IgM Abs and complement that could result in rejection of naive xenografts. After first hamster hearts had been surviving in cobra venom factor (CVF) + CyA-treated rats for 10 days, a time when the anti-donor IgM Ab level was maximal and complement activity had returned to approximately 50% of pretreatment levels, naive hamster hearts or hamster hearts that had been accommodating in another rat for 14 days were transplanted into those rats carrying the surviving first graft. The naive hearts were all hyperacutely rejected. In contrast, a majority of regrafted accommodating hearts survived long-term. There was widespread Ab and activated complement deposition on the vascular endothelium of accommodating first hearts, second accommodating hearts, and rejected second naive hearts. However, only the rejected naive hearts showed extensive endothelial cell damage, myocardial necrosis, fibrin deposition, and other signs of inflammation. Accommodating first and second hearts but not rejected second naive hearts expressed high levels of the protective genes A20, heme oxygenase-1 (HO-1), bcl-2, and bcl-xL. These data demonstrate that accommodated xenografts become resistant to effects of anti-donor IgM Abs and complement that normally mediate rejection of xenografts. We hypothesize that this resistance involves expression by accommodated xenografts of protective genes.
将仓鼠心脏移植到短暂性补体缺失并持续接受环孢素A（CyA）免疫抑制的大鼠体内，尽管抗供体IgM抗体和补体沉积在移植心脏的血管内皮上，但移植心脏仍能长期存活。这种现象被称为“适应性改变”。本研究检验的假设是，发生适应性改变的异种移植物对可导致未适应异种移植物排斥反应的IgM抗体和补体具有抗性。在第一批仓鼠心脏于经眼镜蛇毒因子（CVF）+CyA处理的大鼠体内存活10天后，此时抗供体IgM抗体水平达到最高，补体活性已恢复至预处理水平的约50%，将未适应的仓鼠心脏或已在另一只大鼠体内适应14天的仓鼠心脏移植到携带存活的第一颗移植心脏的大鼠体内。未适应的心脏均发生超急性排斥反应。相比之下，大多数再次移植的适应心脏长期存活。在第一颗适应心脏、第二颗适应心脏以及被排斥的第二颗未适应心脏的血管内皮上均有广泛的抗体和活化补体沉积。然而，只有被排斥的未适应心脏表现出广泛的内皮细胞损伤、心肌坏死、纤维蛋白沉积以及其他炎症迹象。第一颗和第二颗适应心脏而非被排斥的第二颗未适应心脏表达高水平的保护性基因A20、血红素加氧酶-1（HO-1）、bcl-2和bcl-xL。这些数据表明，发生适应性改变的异种移植物对通常介导异种移植物排斥反应的抗供体IgM抗体和补体的作用产生抗性。我们推测这种抗性涉及发生适应性改变的异种移植物对保护性基因的表达。
