CAJ | 학술논문

目的将大鼠胚胎胸腺与后肾原基联合移植至无胸腺裸小鼠,探讨联合移植能否重建受体细胞免疫功能并诱导受者对异种供者器官的特异性免疫耐受的关系.方法从受孕第15天(E15)的Lewis大鼠胚胎中提取胸腺、后肾原基,分别植入BALB/c裸小鼠腹腔右肾包膜下及大网膜内.移植后第10周,行胸腺、后肾移植物的形态学检查及移植后肾的功能检测；并进行外周血T淋巴细胞流式细胞学检测、单向混合淋巴细胞反应(MLR)及皮肤移植试验.结果移植后第10周,移植胸腺及后肾形态发育良好.移植后肾显示一定的排泄功能,联合移植受体双肾切除后的生存时间明显延长(P＜0.05).联合移植受体的外周血T淋巴细胞重建良好；其淋巴细胞对胸腺供体来源的Lewis大鼠脾细胞的刺激呈特异性低反应(P＜0.01)；且胸腺供体来源的大鼠移植皮片平均存活时间明显大于C57BL/6小鼠、BN大鼠移植皮片存活时间(P＜0.01).结论 E15 Lewis大鼠胚胎胸腺、后肾原基联合移植至细胞免疫缺陷的裸小鼠,移植物可生长分化形成器官并发挥功能,受体裸小鼠能重建免疫功能,并有可能诱导对同源供体器官的特异性异种移植免疫耐受.
목적 장대서배태흉선여후신원기연합이식지무흉선라소서,탐토연합이식능부중건수체세포면역공능병유도수자대이충공자기관적특이성면역내수적관계.방법 종수잉제15천(E15)적Lewis대서배태중제취흉선、후신원기,분별식입BALB/c라소서복강우신포막하급대망막내.이식후제10주,행흉선、후신이식물적형태학검사급이식후신적공능검측；병진행외주혈T림파세포류식세포학검측、단향혼합림파세포반응(MLR)급피부이식시험.결과 이식후제10주,이식흉선급후신형태발육량호.이식후신현시일정적배설공능,연합이식수체쌍신절제후적생존시간명현연장(P＜0.05).연합이식수체적외주혈T림파세포중건량호；기림파세포대흉선공체래원적Lewis대서비세포적자격정특이성저반응(P＜0.01)；차흉선공체래원적대서이식피편평균존활시간명현대우C57BL/6소서、BN대서이식피편존활시간(P＜0.01).결론 E15 Lewis대서배태흉선、후신원기연합이식지세포면역결함적라소서,이식물가생장분화형성기관병발휘공능,수체라소서능중건면역공능,병유가능유도대동원공체기관적특이성이충이식면역내수.
Objective To investigate whether the cellular immune function of athymia nude mice can be reestablished and whether the recipients' specific immune tolerance can be induced by the combined xenotransplantation of embryonic thymus and metanephros anlagen from rats to athymia nude mice.Methods Male and female rats were mated overnight.The presence of vaginal plaques was marked as the embryonic day 0(E0).The whole embryos from Lewis rats on embryonic day 15(E15) were taken for the present experiment.The Lewis E15 metanephros and thymus anlagen were taken out from the embryos and immediately preserved in normal saline at 4℃,and then were implanted into the omentum and renal capsule of nude mice.10 weeks post-implantation,the peritoneotomy was carried out on some recipients,metanephros and thymus transplants were removed for histopathological examination.The concentrations of urea nitrogen and creatinine in cyst fluid from the metanephros transplants were measured.The survival time of the recipients was observed after nephrectomy.The blood of the recipients was obtained to detect the re-establishment of T lymphocyte with flow cytometry(FCM).The lymphocyte suspension extracted from recipients were mixed respectively with the spleen cells suspension of Lewis rats,BN rats or C57BL/6 mice to perform mixed lymphocyte reaction(MLR) test.The skins of Lewis rats,BN rats,C57BL/6 and nude mice were transplanted in the chest-back of the recipients to observe the reject reaction.Results 10 weeks post-implantation,both E15 metanephros and thymus transplants were enlarged,and showed well-developed structure under optical microscope and electronic microscope.Metanephros displayed partial excreting function.The concentrations of urea nitrogen and creatinine in cyst fluid from the metanephros transplants were close to the concentrations in the bladder urine.The combined transplant recipients survived longer than the others after nephrectomy(P ＜0.05).The re-establishment of T lymphocyte from the blood of recipients was certified by FCM.MLR indicated that the lymphocyte of the combined transplant recipients had normal reaction to the spleen cells of the BN rats and C57BL/6 mice,but had under-reaction to the donor Lewis's( P＜0.01 ).Survival time of the skin from donor Lewis is longer than that of the BN rats' and the C 5 7 BL/6 mice' s ( P ＜ 0.01 ).Conclusion E15 Lewis metanephros and thymus anlagen heterografted into the athymia nude mice will grow and function well.The nude mice with combined transplantation of E15 Lewis thymus and metanephros anlagen can reestablish immunologic function and may induce tolerance to the metanephros and skin graft from donor Lewis