自体凋亡细胞静脉回输联合雷帕霉素对恒河猴体内调节性T细胞的影响

Effect of intravenous injection of apoptotic cells combined with rapamycin on regulatory T cells in rhesus monkey

目的观察凋亡细胞联合雷帕霉素对恒河猴体内调节性T细胞(Treg)的影响,探讨减少雷帕霉素用量,降低免疫抑制剂副作用的方法。材料及方法以CD4+FOXP3+调节性T细胞比例为观察对象,分组对比实验,4只雄性恒河猴8～10岁龄,体重7～8kg,随机分成实验组和对照组,每组2只。实验组采用低剂量雷帕霉素加凋亡细胞输注的方法,每天给予口服0.4mg雷帕霉素,同时静脉输注凋亡细胞一次;对照组每天给予同样剂量的雷帕霉素,同时静脉注射PBS。定期检测各组恒河猴外周血中CD4+Foxp3+Treg,并计算Treg占CD4+T细胞的比例。对比两组恒河猴Treg变化曲线的异同。结果单纯口服雷帕霉素的恒河猴,Treg/CD4+T比例在1只猴未见明显增加,在第38天为6.92%,另1只仅在4周后明显增加,在第38d为13.7%;而注射凋亡细胞联合雷帕霉素组的恒河猴,其Treg/CD4+T的比例在输注凋亡细胞后2～3周即有明显增加,2只猴在第38d Treg/CD4+T细胞比例升至16.67%和21.56%。结论凋亡细胞联合雷帕霉素有可能升高恒河猴体内Treg的比例。

Objective To investigate the effect of intravenous injection of apoptotic cells combined with rapamycin on regulatory T cells in rhesus monkey and get the methods that decrease the dosage of rapamycin.Materials and methods Rhesus monkeys with 8～10 year old were randomly assigned into experimental and control groups,with 2 animals in each group.Experiments were carried out in the Institute of Transplant Immunology,Zhujiang Hospital,Southern Medical University from December 2008 to March 2009.Four rhesus monkeys were divided into experimental and contaol groups.In the control group,the monkey was injected with PBS,and 0.4 mg of rapamycin was orally administrated daily.In experimental group,apoptotic cells were intravenously injected,and 0.4 mg of rapamycin was orally administrated daily.The percentage of CD4^＋Foxp3＋ Treg in rhesus monkey＇s peripheral blood was detected periodically after operation,and the percentage of Treg in CD4^＋T cells was accordingly calculated.The changes of Treg in two groups of rhesus monkeys were compared.Results Apoptotic cells combined with rapamycin might be able to raise the percentage of Treg in CD4^＋ T cells in rhesus monkey.In the two monkeys administrated with rapamycin,the percentages of Treg/CD4^＋T cells was increased only in one monkey.In control group,38 days after the first administration of rapamycin,Treg/CD4^＋T cells were increased only to 13%and 6.92%,respectively.In the two monkeys adminitrated with apoptotic cells and rapamycin,the Treg percentages was increased to 21.56%and 16.67%2 or 3 weeks after injecting apoptotic cells.Conclusion Treatment with apoptotic cells in combination with rapamycin might be able to increase the percentage of Treg in rhesus monkey.