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目的探索更为温和的适合临床应用的诱导异种移植耐受的方案。方法给小剂量照射（ 300 rad）的 C57BL/6 (B6)小鼠静脉注射抗小鼠 CD4单抗 0.5 ml后输注 Lewis大鼠骨髓细胞 ,并联合应用腹腔注射环磷酰胺诱导耐受。于耐受诱导后 30 d对受体小鼠作耐受状态的检查，包括供体特异性皮肤移植、混合淋巴细胞反应（ MLR）及迟发型超敏反应（ DTH）。并通过过继转移实验、外源 IL- 2对耐受小鼠供体特异性 MLR的影响等进一步探讨耐受形成的机制。结果 Lewis大鼠的皮肤移植物在耐受 B6小鼠中存活期特异性延长， MLR及 DTH检查证明 B6小鼠对 Lewis大鼠的脾细胞产生特异性耐受，对无关第三者 DA大鼠及 BALB/c小鼠的脾细胞仍表现出强烈的免疫应答。体内外过继转移实验表明 ,耐受不能被转移 ,未发现抑制细胞的存在。耐受小鼠供体特异的 MLR可以被外源 IL- 2逆转 ,说明耐受主要不是克隆排除，而与克隆不应答有关。结论应用低剂量照射、骨髓移植、环磷酰胺及抗 CD4单抗等方法法可以有效诱导出小鼠对大鼠的移植耐受。
OBJECTIVE: To explore a milder approach to induce xenograft tolerance suitable for clinical use. Methods C57BL / 6 (B6) mice (300 rad) were injected intraperitoneally with 0.5 ml anti-mouse monoclonal antibody (mAb) and then infused Lewis rat bone marrow cells. Induction of tolerance was induced by intraperitoneal injection of cyclophosphamide. The recipient mice were examined for tolerance status 30 days after tolerance induction, including donor-specific skin grafts, mixed lymphocyte reaction (MLR) and delayed-type hypersensitivity (DTH). The mechanisms of tolerance formation were further explored by adoptive transfer experiments and the effect of exogenous IL-2 on donor-specific MLR in mice. Results The skin grafts of Lewis rats were specifically prolonged in the tolerant B6 mice. The results of MLR and DTH showed that B6 mice had specific tolerance to Lewis rat spleen cells. And spleen cells of BALB / c mice still showed a strong immune response. In vitro and in vivo adoptive transfer experiments show that tolerance can not be transferred, did not find the presence of inhibitory cells. MLR tolerated mouse donor-specific can be reversed by exogenous IL-2, indicating that tolerance is not primarily cloned but not cloned. Conclusion Low dose irradiation, bone marrow transplantation, cyclophosphamide and anti-CD4 monoclonal antibody method can effectively induce the mice transplantation tolerance.