髓源性树突状细胞过继转移诱导1型糖尿病小鼠免疫耐受及其机制  

Immune tolerance and its mechanism induced by adoptive transfer of bone marrow-derived dendritic cells in mice with insulin-dependent diabetes mellitus

作　　者：张程亮[1] 向明[1] 邹晓蕾[1] 彭佳蓓[1] 

机构地区：[1]华中科技大学同济医学院药学院药理室,湖北省武汉市430030

出　　处：《世界华人消化杂志》2006年第33期3175-3179,共5页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30200343~~

摘　　要：目的:探讨髓源性树突状细胞(DC)过继转移诱导1型糖尿病(IDDM)小鼠免疫耐受的作用及其机制.方法:体外培养BALB/c小鼠骨髓来源DC,测定纯度,经ip小鼠体内.随后,采用少量多次链脲佐菌素(STZ)ip的方法建立IDDM小鼠模型.每周测定血糖,第4周时处死动物,分离脾脏淋巴细胞并进行体外培养,MTT法测定小鼠脾淋巴细胞增殖反应,采用流式细胞术检测CD4+CD25+调节性T细胞.ELISA法测定血清IL-2,IL-4含量.结果:过继转移表达CD11c+的DC4wk后,小鼠的血糖可明显降低,与模型对照组有极显著差异(8.32±1.05mmol/Lvs18.36±1.55mmol/L,P<0.01).与模型对照相比,过继转移DC可使小鼠脾淋巴细胞增殖能力降低(0.264±0.019vs0.489±0.012,P<0.05),流式细胞术测定结果显示CD4+CD25+T细胞亚群比例上升到5.28%,而模型对照组仅1.56%.DC过继可有效抑制IL-2分泌(121±19ng/Lvs195±32ng/L,P<0.05),而提高IL-4含量(187±36ng/Lvs76±30ng/L,P<0.01).结论:过继转移髓源性DC可以诱导免疫耐受防止IDDM的发生,其机制与促进体内CD4+CD25+T细胞亚群产生,重建Th1/Th2细胞因子平衡相关.AIM： To investigate immune tolerance induced by adoptive transfer of bone marrowderived dendritic cells （DCs） in mice with type 1 diabetes, and to explore its underlying mechanism. METHODS： Bone marrow cells from BALB/c mice were used to generate DCs by in vitro coculturing with cytokines. After identifying the purity of DCs, We injected the cells into BALB/c mice intraperitoneally. The mouse model of type 1 diabetes was established by injecting low dose of streptozotocin （STZ） for 5 consecutive days. The blood glucose was examined once a week.At the end of the 4^th week, all the mice were killed and splenic lymphocytes were collected. After in vitro culturing, the proliferation of lymphocytes was detected by MTT assay, and the proportion of CD4^＋CD25^＋T cells was analyzed by fluorescence activated cell sorter （FACS）. The serum levels of cytokines IL-2 and IL-4 were determined by enzyme-linked immunosorbent assay （ELISA）. RESULTS： The level of blood glucose was decreased significantly after adoptive transfer of DCs in comparison with that in the model controls （8.32 ± 1.05 mmol/L vs 18.36 ± 1.55 mmol/L, P 〈 0.01）. In vitro, the proliferation of splenic lymphocytes was inhibited as compared with that of the model controls （0.264 ± 0.019 vs 0.489 ± 0.012, P 〈 0.05） while the proportion of CD4^＋CD25^＋ T cells was enhanced to 5.28% （1.56% in the model controls）. Adoptive transfer of DCs effectively suppressed the secretion of IL-2 （121 ± 19 ng/L vs 195 ± 32 ng/L, P 〈 0.05） while elevated the content of IL-4 （187 ± 36 ng/L vs 76 ± 30 mg/L, P 〈 0.01）. CONCLUSION： Adoptive transfer of bone marrow-derived DCs can induce the immune tolerance to type 1 diabetes in mice, and the mechanism may be related with the production of CD4^＋CD25^＋ T cells and balance between Thl and Th2 cytokines.

关 键 词：树突状细胞 1型糖尿病 免疫耐受 调节性 T细胞 

分 类 号：R587.1[医药卫生—内分泌]