【摘要】 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。更多还原

【Abstract】 To explore a moderate and effective project which will be clinically suitable to induce donor- specific tolerance across xenogeneic barriers. Methods 4× 107 Lewis rat bone marrow cells were infused to 300 rad total body irradiated (TBI) C57BL/6 (B6) mice, combined with intraperitoneal administration of cyclophosphamide (CTX) and intravenous injection of anti- mouse CD4 monoclonal antibody. Recipient B6 mice were characterized for the tolerance status with donor Lewis rat skin graft, mixed lymphocyte reaction (MLR), and delayed- type hypersensitivity (DTH) assays after 30 days. Adoptive transfer and the effect of IL- 2 on MLR were detected to further explore the tolerance mechanism. Results Survival time of donor rat skin grafts was specifically prolonged in the tolerant B6 mice. The results of MLR and DTH assays showed donor- specific hyporeactivity, while the tolerant B6 mice were still immunocompetent to MHC- disparate third party BALB/c mouse or DA rat stimulator cells. Conclusions A reliable xenogeneic transplantation tolerance of mouse to rat was achieved by this project of tolerance induction. The result of in vitro and in vivo adoptive transfer of spleen cells from tolerant B6 mice demonstrated that the sup pressor cells were unlikely to exert effect in the tolerance. The inhibition of specific MLR could be reversed by adding IL- 2, indicating that clonal anergy instead of clonal deletion is responsible for the tolerant maintenance.更多还原