CAJ | 학술논문

背景:诱导供者特异性免疫耐受被认为是最终克服器官移植后排斥反应的有效途径,近年来关于未成熟树突状细胞在诱导免疫耐受中的重要作用日益受到关注.目的:观察他克莫司处理的供者未成熟树突状细胞对大鼠同种异体心脏移植免疫耐受的影响,分析未成熟树突状细胞诱导免疫耐受的作用途径.设计:随机对照动物实验.材料:实验于2006-04/2006-12在青岛大学医学院附属医院动物实验中心完成.以45只Wistar大鼠为供体,45只SD大鼠为受体,行颈部心脏移植45例次.按随机数字表法分为3组,每组15例次,进行不同的预处理.方法:对照组、未经他克莫司处理组及他克莫司处理组移植前7 d分别经尾静脉注射生理盐水、供者未成熟树突状细胞和他克莫司处理的未成熟树突状细胞.分别测定移植后SD大鼠与Wistat 大鼠及第3品.系Lewis大鼠的单向混合淋巴细胞反应.主要观察指标:各组受体大鼠移植心脏存活时间、心肌病理及血清白细胞介素2、白细胞介素4、白细胞介素10、Y-干扰素含量变化.结果:①未经他克莫司处理组大鼠的移植心脏存活时间较对照组明显延长(P＜0.01),他克莫司处理组大鼠的移植心脏存活时间进一步延长(P＜0.05).②混合淋巴细胞培养结果显示为供者特异性.③各组大鼠血清白细胞介素2、Y-干扰素、白细胞介素4、白细胞介素10含量差异具有显著性意义(P＜0.01).代表Th1的白细胞介素2、Y-干扰素水平明显降低,代表Th2的白细胞介素4、自细胞介素10水平明显增高.结论:未成熟树突状细胞能够诱导同种异体大鼠心脏移植免疫耐受;他克莫司处理的未成熟树突状细胞能够加强这种免疫耐受,且这种耐受是供者特异性的.其可能主要通过调节T细胞免疫应答类型(Th1至Th2的免疫偏移)、诱导调节性T细胞和诱导T细胞失能等途径来参与免疫耐受的形成. 揹景:誘導供者特異性免疫耐受被認為是最終剋服器官移植後排斥反應的有效途徑,近年來關于未成熟樹突狀細胞在誘導免疫耐受中的重要作用日益受到關註.目的:觀察他剋莫司處理的供者未成熟樹突狀細胞對大鼠同種異體心髒移植免疫耐受的影響,分析未成熟樹突狀細胞誘導免疫耐受的作用途徑.設計:隨機對照動物實驗.材料:實驗于2006-04/2006-12在青島大學醫學院附屬醫院動物實驗中心完成.以45隻Wistar大鼠為供體,45隻SD大鼠為受體,行頸部心髒移植45例次.按隨機數字錶法分為3組,每組15例次,進行不同的預處理.方法:對照組、未經他剋莫司處理組及他剋莫司處理組移植前7 d分彆經尾靜脈註射生理鹽水、供者未成熟樹突狀細胞和他剋莫司處理的未成熟樹突狀細胞.分彆測定移植後SD大鼠與Wistat 大鼠及第3品.繫Lewis大鼠的單嚮混閤淋巴細胞反應.主要觀察指標:各組受體大鼠移植心髒存活時間、心肌病理及血清白細胞介素2、白細胞介素4、白細胞介素10、Y-榦擾素含量變化.結果:①未經他剋莫司處理組大鼠的移植心髒存活時間較對照組明顯延長(P＜0.01),他剋莫司處理組大鼠的移植心髒存活時間進一步延長(P＜0.05).②混閤淋巴細胞培養結果顯示為供者特異性.③各組大鼠血清白細胞介素2、Y-榦擾素、白細胞介素4、白細胞介素10含量差異具有顯著性意義(P＜0.01).代錶Th1的白細胞介素2、Y-榦擾素水平明顯降低,代錶Th2的白細胞介素4、自細胞介素10水平明顯增高.結論:未成熟樹突狀細胞能夠誘導同種異體大鼠心髒移植免疫耐受;他剋莫司處理的未成熟樹突狀細胞能夠加彊這種免疫耐受,且這種耐受是供者特異性的.其可能主要通過調節T細胞免疫應答類型(Th1至Th2的免疫偏移)、誘導調節性T細胞和誘導T細胞失能等途徑來參與免疫耐受的形成.
배경:유도공자특이성면역내수피인위시최종극복기관이식후배척반응적유효도경,근년래관우미성숙수돌상세포재유도면역내수중적중요작용일익수도관주.목적:관찰타극막사처리적공자미성숙수돌상세포대대서동충이체심장이식면역내수적영향,분석미성숙수돌상세포유도면역내수적작용도경.설계:수궤대조동물실험.재료:실험우2006-04/2006-12재청도대학의학원부속의원동물실험중심완성.이45지Wistar대서위공체,45지SD대서위수체,행경부심장이식45례차.안수궤수자표법분위3조,매조15례차,진행불동적예처리.방법:대조조、미경타극막사처리조급타극막사처리조이식전7 d분별경미정맥주사생리염수、공자미성숙수돌상세포화타극막사처리적미성숙수돌상세포.분별측정이식후SD대서여Wistat 대서급제3품.계Lewis대서적단향혼합림파세포반응.주요관찰지표:각조수체대서이식심장존활시간、심기병리급혈청백세포개소2、백세포개소4、백세포개소10、Y-간우소함량변화.결과:①미경타극막사처리조대서적이식심장존활시간교대조조명현연장(P＜0.01),타극막사처리조대서적이식심장존활시간진일보연장(P＜0.05).②혼합림파세포배양결과현시위공자특이성.③각조대서혈청백세포개소2、Y-간우소、백세포개소4、백세포개소10함량차이구유현저성의의(P＜0.01).대표Th1적백세포개소2、Y-간우소수평명현강저,대표Th2적백세포개소4、자세포개소10수평명현증고.결론:미성숙수돌상세포능구유도동충이체대서심장이식면역내수;타극막사처리적미성숙수돌상세포능구가강저충면역내수,차저충내수시공자특이성적.기가능주요통과조절T세포면역응답류형(Th1지Th2적면역편이)、유도조절성T세포화유도T세포실능등도경래삼여면역내수적형성.
BACKGROUND: Immune tolerance is regarded as the most effective measure to overcome rejection. For the past few years, the important effect of immature dendritic cells (imDCs) on immune tolerance has drawn close attention. OBJECTIVE: To study the effect of imDCs treated with tacrolimus (FK506) on imlnune tolerance in rat allograft organ transplantation and to investigate the mechanism of immune tolerance induced by imDCs. DESIGN: A randomized and controlled animal experiment. MATERIALS: The experiment was carried out at the Experimental Animal Center, the Affiliated Hospital of Medical College. Qingdao University from April 2006 to December 2006.Cervical heart transplantations were performed in which 45Wister rats were used as donors and45 SD rats as allograft recipients. The ratswere randomly divided into three groups with 15 for each. METHODS: Normal sodium, imDes. and imDCs treated with FK506 were injected via vena caudalis seven. days before the operations respectively. Mixed lymphocyte reaction (MLR) was meas ured on SD, Wistar, and Lewis rats. MAIN OUTCOME MEASURES: Heart allografi survival was monitored and one-way MLR, heart pathology and the levels of interleukin-2(IL-2),IL-4,IL-10,and interferon-Y(IFN-Y)in the serum were detected. RESULTS: In treatment group without FK506.heart allografl survival were prolonged after imDC injection(P＜0.01);while their survival were prolonged further in treatment group with FK506(P＜0.05).MLR showed that the tolerance was donor specific. Analysis of variance showed that tere was high significant difference for serum concentrations of IL-2,IFN-Y,IL-4,and IL-10 in the three groups(P＜0.01).The concentrations of IL-2 and IFN-Y expressing on Th1 were lower. and that of IL-4 and IL-10 expressing on Th2 were obviously higher in the latter two groups. CONCLUSION: ImDCs can induce immune tolerance in rat heterotopic heart transplantation successfully; ImDCs treated with FK506 can enhance the tolerance which is donor specific.ImDCs may induce the immnune tolerance bymeans of modifying the immune response type of T cells (immune deflection from Th1 to Th2), mediating the generation of regulatory T cells (T-reg)and inducing T cells disenabling.