输注调节性T细胞延缓非肥胖糖尿病小鼠糖尿病的发生

Infusion of regulatory T cells delayed the development of autoimmune diabetes in non-obese diabetic mice

目的观察过继输注调节性T细胞（Treg）对非肥胖糖尿病（NOD）小鼠自发性糖尿病发生的影响。方法分选NOD小鼠天然调节性T细胞（nTreg），并诱导Naive T细胞转化为CD4^＋CD25^＋ Foxp3^＋调节性T细胞（iTreg），分别输注予4周龄的雌性NOD小鼠，观察糖尿病的发生情况，并确定细胞输注后Treg在体内的分布、检测血清中TGF-β1、IL-10及IL-4的表达以探讨Treg的作用机制。结果对照组小鼠13周龄时即100％自发性发生糖尿病，而输注iTreg和nTreg分别能延缓糖尿病的发生时间至24周龄和25周龄，与对照组比较差异有统计学意义（P〉0．05）。Treg细胞输注后主要分布在胸腺，iTreg在体内能促进TGF-β1、IL-10及IL-4表达的上调[血中浓度分别为（543．00±26．51）、（107．67±12．66）、（93．33±12．58）ng／L]，与对照组比较差异有统计学意义[（60．67±15．82）、（20．67±6．03）、（30．67±5．51）ng／L，P〈0．05]。结论在体外诱导生成的调节性T细胞可延缓NOD小鼠糖尿病的发生，其机制与上调具有免疫抑制效应的细胞因子相关。

Objective To investigate the effects on the development of autoimmune diabetes by infusing regulatory T cells （Treg cells） in non-obese diabetic （NOD） mice. Methods Natural Treg cells （nTreg） were isolated and Naive T cells were induced into CD4^＋ CD25^＋ Foxp3^＋ Treg cells （iTreg）. nT- leg and iTreg cells were infused into 4-week-old female mice respectively. The development of autoimmune diabetes,distribution of Treg ceils in the NOD mice after infusion, and the serum level of transforming growth factor-β1 （ TGF-β1 ） , intedeukin-10 （IL-10） and interleukin-4 （ IL-4 ） were observed. Results The mice infused with nTreg or iTreg cells developed autoimmune diabetes at 24 or 25 weeks old respec- tively. The time of autoimmune diatetes development was significantly delayed in nTreg or iTreg cells treated mice as compared with the untreated NOD mice （P 〈0.05 ） which developed autoimmune diabetes at 13 weeks old. Treg cells were distributed into thymus after being infused into NOD mice. The euncentra- tions of TGFo[31 ,IL-10 and IL-4 in iTreg cells treated mice were （543.00 ±26.51 ）, （ 107.67 ± 12.66） and （93.33 ± 12.58） ng/L,which were significantly upreguated as compared with those in untreated mice （ P 〈 0.05 ）, which were （ 60.67 ± 15.82 ）, （ 20.67 ± 6.03 ） and （ 30.67 ± 5.51 ） ng/Lm, respectively. Conclusion Infusion of the Treg cells can delay the development of autoimmune diabetes in NOD mice by up-regulating, the expression of TGF-β1 .IL-10 and IL-4.