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目的比较钙调磷酸酶抑制剂[环孢素A(CsA)和他克莫司(FK506)]与西罗莫司(SRL))对CD4~+CD25~+免疫调节性T细胞(CD4~+CD25~+Tregs)及其细胞表面标志性因子细胞毒T淋巴细胞相关抗原4(CTLA-4)和又状头/翅膀状螺旋转录因子(Foxp3)的影响,为临床合理选择免疫抑制方案提供依据。方法选择2004年1月至4月行肾移植的患者30例,男女不限,年龄20～50岁,随机分为3组,每组10例。(1)CsA组:免疫抑制方案为CsA+霉酚酸酯(MMF)+泼尼松(Pred);(2)FK506组:免疫抑制方案为FK506+MMF+Pred;(3)SRL组:免疫抑制方案为SRL+ MMF+Pred;3组的免疫诱导治疗方案均相同。各组分别于术前、术后半年、1年、2年取血样检测CD4~+CD25~(+high)/CD4~+T细胞比值及CD4~+CD25~(high)T细胞表面CTLA-4和Foxp3的表达率;比较3组治疗方案对各项指标的影响。结果应用3种不同的免疫抑制方案后,各组受者CD4~+CD25~(+high)/ CD4~+T细胞比值及CD4~+CD25~(high)T细胞表面CTLA-4和Foxp3的表达率均明显低于术前,虽然半年后有所上升,但CsA和FK506组各项指标上升明显较SRL组慢,SRL组各项指标恢复水平明显优于钙调磷酸酶抑制剂组。结论SRL与钙调磷酸酶抑制剂比较,对CD4~6CD25~+Treg细胞影响明显较轻,可能对器官移植术后移植免疫耐受的诱导和维持有促进作用。
Objective To compare the effects of calcineurin inhibitors (CsA and FK506) and sirolimus (SRL) on CD4 ~ + CD25 ~ + immunoregulatory T cells (CD4 ~ CD25 + Tregs and its cell surface marker cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and like head / wing spiral transcription factor (Foxp3) in order to provide a basis for the clinical selection of immunosuppressive regimens . Methods Thirty patients undergoing renal transplantation between January 2004 and April 2004 were enrolled in this study. The age ranged from 20 to 50 years. They were randomly divided into 3 groups (10 in each group). (2) FK506 group: FK506 + MMF + Pred; (3) SRL group: immunosuppression The protocol was SRL + MMF + Pred; the immunization induction regimens were the same in all three groups. The percentages of CD4 ~ + CD25 ~ (+ high) / CD4 ~ + T cells and the expression of CTLA-4 on CD4 ~ + CD25 ~ (high) T cells were measured before and 6 months, 1 year and 2 years after operation. And Foxp3 expression rates; the impact of the three groups of treatment programs on the indicators. Results After applying 3 different immunosuppressive regimens, the ratios of CD4 ~ + CD25 ~ (+ high) / CD4 ~ + T cells and the expression of CTLA-4 and Foxp3 on CD4 ~ + CD25 ~ The rates of CsA and FK506 group were significantly higher than that of SRL group, and the indexes of SRL group were significantly better than those of calcineurin inhibitor group. Conclusion Compared with calcineurin inhibitor, SRL has a significantly lower effect on CD4 ~ +6 CD25 ~ + Treg cells and may promote the induction and maintenance of immune tolerance after transplantation.