小鼠到大鼠骨髓移植诱导供者特异的免疫耐受

Study on the induction of donor-specific immunologic tolerance of mouse to rat xenogenic bone marrow transplantation

目的 探索适用临床的异种骨髓移植诱导免疫耐受的方案。方法 受体SD大鼠接受亚致死剂量照射(5 5Gy)当天尾静脉注射BALB/c小鼠骨髓细胞 8× 10 7,2d后腹腔内注射环磷酰胺 15 0mg/kg。分别于移植后 3 0 ,60及90d取受体大鼠外周血 ,用特异性单抗作直接免疫荧光染色后上流式细胞仪 (FACS)分析 ,检测骨髓植入的嵌合情况 ,并于 4周后作皮片移植和混合淋巴反应 (MLR) ,检查免疫耐受情况。结果 受体大鼠外周血可检测到小鼠骨髓源性细胞 ,嵌合体在 90d时仍存在。皮片移植和MLR证明受体SD大鼠对供体BALB/c小鼠产生特异性免疫耐受 ,对无关第 3者C5 7BL/ 6小鼠仍有强烈免疫应答。结论 小鼠到大鼠骨髓移植成功地诱导了特异性免疫耐受。

Objective To establish an effective protocol for potential clinical usage in inducing donor-specific immunologic tolerance across xenogenic barrier. Methods SD rats were conditioned with 5 5Gy sublethal total body irradiation(TBI), followed by infusion of 8×10 7 BALB/c mice bone marrow cells(BMC) on day 0,and then were administered intraperionially 150 mg/kg of cyclophosphamide (Cy) on day 2. Recipients were detected for the percentage of mouse origin cells in the peripheral blood white cells by using fluorescence activated cell sorter(FACS) on day 30, 60, 90.Skin grafting and mixed lymphocyte reaction(MLR) were performed to determine the tolerance status. Results Mouse lymphoid cells were reliably present in SD rats for more than 90 days. Recipients were specially tolerant to donor xenoantigens in skin grafting and MLR assays, while maintaining immunocompetent to MHC-disparate third party C57BL/6 mouse.Conclusion Donor-specific immunologic tolerance can be successfully induced in mouse to rat xenogeneic BMC transplantation.