CAJ | 학술논문

目的探讨姜黄素(Cur)处理的树突状细胞(DC)诱导同种T淋巴细胞低反应性的效果以及对大鼠移植肾存活时间的影响.方法体外培养Wistar大鼠骨髓来源的DC,经Cur处理后,以流式细胞仪检测细胞CD11c、CD80、CD86及主要组织相容性复合物(MHC)Ⅱ类抗原的变化,酶联免疫吸附试验测定DC分泌白细胞介素12(IL-12)的水平,混合淋巴细胞反应(MLR)检测其刺激Lewis大鼠T淋巴细胞增殖的能力,二次MLR测定其诱导的T淋巴细胞抗原特异性低反应性.以Wistar大鼠为供者,Lewis大鼠为受者,进行肾移植.术前第7天,经尾静脉给受者输注用Cur处理的供者DC,分设不处理对照组和未成熟DC对照组(经尾静脉注射供者的未成熟DC),术后观察移植肾存活时间及组织学改变情况,第14天检测受者T淋巴细胞对供者成熟DC的反应性.结果 Cur能明显抑制DC共刺激分子CD11c、CD80、CD86及MHCⅡ类抗原的表达以及IL-12的分泌(P＜0.05).同种T淋巴细胞对经Cur处理过的DC刺激的增殖能力明显减低,且这种低反应性具有抗原特异性.对照组和未成熟DC对照组移植肾的存活时间分别为(8.6±2.1)d和(22.4±7.4)d,实验组为(31.5±6.9)d,实验组移植肾存活时间明显长于对照组和未成熟DC对照组(P＜0.05),且其移植肾组织的损伤程度最轻.实验组受者的T淋巴细胞对供者成熟DC刺激的反应性明显低于对照组(P＜0.05),而对第三方无关抗原的刺激保持较高增殖强度.结论 Cur能抑制DC成熟功能,诱导供者特异性的T淋巴细胞低反应性,移植前输注经Cur处理的未成熟DC能显著延长大鼠移植肾的存活时间.
목적 탐토강황소(Cur)처리적수돌상세포(DC)유도동충T림파세포저반응성적효과이급대대서이식신존활시간적영향.방법 체외배양Wistar대서골수래원적DC,경Cur처리후,이류식세포의검측세포CD11c、CD80、CD86급주요조직상용성복합물(MHC)Ⅱ류항원적변화,매련면역흡부시험측정DC분비백세포개소12(IL-12)적수평,혼합림파세포반응(MLR)검측기자격Lewis대서T림파세포증식적능력,이차MLR측정기유도적T림파세포항원특이성저반응성.이Wistar대서위공자,Lewis대서위수자,진행신이식.술전제7천,경미정맥급수자수주용Cur처리적공자DC,분설불처리대조조화미성숙DC대조조(경미정맥주사공자적미성숙DC),술후관찰이식신존활시간급조직학개변정황,제14천검측수자T림파세포대공자성숙DC적반응성.결과 Cur능명현억제DC공자격분자CD11c、CD80、CD86급MHCⅡ류항원적표체이급IL-12적분비(P＜0.05).동충T림파세포대경Cur처리과적DC자격적증식능력명현감저,차저충저반응성구유항원특이성.대조조화미성숙DC대조조이식신적존활시간분별위(8.6±2.1)d화(22.4±7.4)d,실험조위(31.5±6.9)d,실험조이식신존활시간명현장우대조조화미성숙DC대조조(P＜0.05),차기이식신조직적손상정도최경.실험조수자적T림파세포대공자성숙DC자격적반응성명현저우대조조(P＜0.05),이대제삼방무관항원적자격보지교고증식강도.결론 Cur능억제DC성숙공능,유도공자특이성적T림파세포저반응성,이식전수주경Cur처리적미성숙DC능현저연장대서이식신적존활시간.
Objective To study the efficacy of hypo responsiveness of allogenic T cells induced by curcumin (Cur)-treated dendritic cells (DCs) and influence on survival time of renal allografts in rats.Methods DCs were generated from Wistar rat bone marrow and treated with Cur. The costimulatory molecules (CDl1c, CD80, CD86 and major histocompability complex Ⅱ ) were determined by using flow cytometry,and the production of IL-12 in DCs culture supernatant was examined by using ELISA.The probability of Cur treated DCs to stimulate the proliferation of Lewis rat T cells was detected by using mixed leukocyte reaction (MLR),and the antigen specific T cell hypo responsiveness was analyzed by using secondary MLR. Allograft renal transplantation animal models were established by using Wistar rats as donors,and Lewis rats as recipients.At 7th day before allograft renal transplantation,Cur-treated DCs from donors were injected into recipients through tail vein, meanwhile the non-treated control group and immature DCs control group (immature DCs from donors were injected into recipients through tail vein) were set up.The allograft survival time and allograft pathology after transplantation were assayed.Reaction of T cells from the recipients to mature DCs of donors was analyzed at 14th day.Results Cur restrained the expression of DCs phcnotypc and production of IL-12 (P＜0.05). Cur treated DCs displayed poor ability to stimulate T cells proliferation,and potential to induce antigen specific T cell hypo-responsiveness.The survival time of the renal allograft in Cur-treatcd CDs group [(31.5 ± 6.9) days] was significantly longer (P＜0.05) than in control group [(8.6± 2.1) days] and immature DCs control group [(22.4± 7.4) days],and the pathological lesions in the renal allografts in Cur treated CDs group were milder than in the control group and immature DCs control group.T cells from the recipients injected with Cur-treated DCs showed significant hypo-responsiveness to mature DCs from donors (P＜0.05),but higher proliferation ability to the stimulation of third party independent antigen.Conclusion Cur can suppress the maturation and function of DCs,and induce immune suppression of allogeneic T cells,while infusion of Cur-treated immature DCs can prolong the survival of renal allograft remarkably.