大鼠→小鼠异种骨髓移植耐受诱导的研究  

Study on the induction of xenogeneic tolerance of rat to mouse bone marrow trans

作　　者：宋娴媛[1] 苑学礼[2] 谢蜀生[1] 

机构地区：[1]北京医科大学免疫学系,100083 [2]北京医科大学第一医院泌尿外科北京医科大学泌尿外科研究所

出　　处：《中华血液学杂志》1999年第8期409-412,共4页Chinese Journal of Hematology

基　　金：国家自然科学基金

摘　　要：目的 探索适合临床应用的有效诱导异种骨髓移植耐受的方案。方法 给亚致死照射（５Ｇｙ） 的Ｃ５７ＢＬ／ ６ （Ｂ６） 小鼠尾静脉注射４ ×１０７ Ｌｅｗｉｓ 大鼠骨髓细胞，２ 天后腹腔注射环磷酰胺１５０ｍｇ／ｋｇ 。分别于骨髓移植后３０ 天、６０ 天、９０ 天，对受体小鼠外周血、脾脏及胸腺中的淋巴细胞进行间接免疫荧光染色， 作ＦＡＣＳ 分析， 检测大鼠源性的骨髓细胞在小鼠体内植活情况，并于３０ 天后，对受体小鼠作混合淋巴细胞反应（ ＭＬＲ） 及迟发超敏反应（ＤＴＨ） 检查。结果 经处理的Ｂ６ 小鼠外周血、脾脏及胸腺中检测出了大鼠源性的骨髓嵌合体， 嵌合体可长期存在（ ＞ ３ 个月） 。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３ 者ＤＡ 大鼠及ＢＡＬＢ／ ｃ 小鼠的脾细胞仍表现出强烈的免疫应答。结论 在Ｂ６ 小鼠体内成功地诱导出了供者特异性的大鼠→小鼠异种骨髓移植耐受。Objective To establish an effective protocol for potential clinical usage in inducing donor specific tolerance across xenogeneic barriers. Methods C57BL/6 (B6) mice were conditioned with 5 Gy sublethal total body irradiation (TBI), followed by infusion of 4×107 Lewis rat bone marrow cells on day 0, then were intraperitonially administered 150 mg/kg cyclophosphamide (CP) on day 2. Recipients were characterized for engraftment with xenogeneic bone marrow cells by using fluorescence activated cell sorter (FACS) to determine the percentage of rat origin cells in the peripheral blood lymphocytes(PBL), splenic and thymic lymphoid cells on day 30, 60 and 90. Mixed lymphocyte reaction (MLR) and delayed type hypersensitivity (DTH) assay were performed on day 30 to examine the tolerance status. Results Rat lymphoid chimeras were reliable present in the tolerant B6 mice for more than 3 months. B6 recipients were specifically tolerant to host xenoantigens in MLR and DTH assays, but were still immunocompetent to MHC disparate third party BALB/c mouse or DA rat stimulator cells. Conclusion A durable rat to mouse xenogeneic bone marrow transplantation tolerance was achieved in this modal.

关 键 词：嵌合体 免疫耐受 骨髓移植 异种移植 

分 类 号：R457.7[医药卫生—治疗学]