抗CD25单克隆抗体对肾移植受者CD4~+ CD25~(high)调节性T细胞的影响

目的 评价抗CD25单克隆抗体对肾移植受者术后早期CD4~+ CD25~(high)调节性T细胞(CD4~+ CD25~(high)Treg)的影响.方法 2007年2-9月接受初次亲属活体供肾移植的受者41例,根据是否使用抗CD25单克隆抗体(商品名daclizumab)分为抗体组(21例)和对照组(20例).其中抗体组在肾移植术前2h及术后第14天分别给予抗CD25单抗各50mg.在移植前及移植后第13、17、60天分别留取肝素抗凝外周血15ml.应用流式细胞仪测定两组受者外周血CD4~+T细胞和CD4~+ CD25~(high)Treg比例的变化,半定量RTPCR检测CD25 mRNA的表达变化.结果 肾移植术后13、17、60d抗体组的CD25~+ T细胞占CD4~+ T细胞的比例(20%±8%、13%±7%、24%±9%)低于对照组(45%±6%、41%±5%、40%±6%),差异有统计学意义(P<0.05).抗体组术后第17天CD4~+ CD25~(high)Treg占CD4~+ T细胞的比例为4.40%±0.26%,明显低于对照组(8.56%±0.36%,P<0.01);而术后13、60d抗体组CD4~+ CD25~(high)Treg所占比例分别为7.00%±0.47%、3.75%±0.19%,与对照组(分别为8.04%±0.32%、3.66%±0.31%)比较差异无统计学意义(P>0.05).抗体组CD25 mRNA相对表达水平在给予第二次抗体前(术后第13天)为1.65±0.22,术后第17天为1.84±0.27,两者间差异无统计学意义(P>0.05).对照组术后第17天CD25 mRNA相对表达水平为1.70±0.23,与抗体组比较差异无统计学意义(P>0.05).结论 两剂共100mg抗CD25单抗仅一过性地降低CD4~+ CD25~(high)Treg,不会影响其活化扩增,无损于术后早期的免疫耐受诱导及维持.

Effects of anti-CD25 monoclonal antibody on CD4~+ CD25~(high) regulatory T cells in recipient of kidney transplantation

Objective To assess the effect of the anti-CD25 monoclonal antibody (anti-CD25mAb)on CD4~+CD25~(high) regulatory T cells(CD4~+ CD25~(high) Treg cells) in recipient at the early stage of kidney transplantation. Methods Forty-one renal transplant recipients who primarily received the donors kidney of their relatives during Feb .to Sep. of 2007 were assigned to Antibody group (21 cases) and Control group (20 cases) according to the usage of anti-CD25 monoclonal antibody (daclizumab).Recipients in Antibody group were respectively given 50 mg daclizumab 2h before and 14d after the renal transplantation, and 15 ml of heparin treated peripheral blood were taken before and 13th,17th and 60th day after the transplantation, the proportion of CD4~+ T cells and CD4~+ CD25~(high) Treg in the recipients peripheral blood of the both groups was determined by flow cytometry, and the expression of CD25 mRNA was detected by semiquantitative RT-PCR Results On the 13th,17th and 60th day after renal transplantation, the proportion of CD4~+ CD25~+ cells in total CD4~+ T cells was significantly lower in Antibody group(20±8%,13±7%and 24±9%)than in Control group (45±6%,20±8%and 41±5%,vs 13±7%,P<0.05).The proportion of CD4~+ CD25~(high) Treg in total CD4~+ T cells was 4.40%±0.26% in Antibody group 17th day after renal transplantation,significantly lower than that in control group(8.56%±0.36%,P<0.01),while no significant difference was found on the proportion of CD4~+ CD25~(high) Treg in total CD4~+ T cells on the 13th and 60th day after transplantation between Antibody group (7.00%±0.47%and 3.75%±0.19%)and Control group(8.04%±0.32%and 3.66%±0.31%,P>0.05).The relative expression levels of CD25 mRNA in Antibody group were 1.65±0.22 and 1.84±0.27,respectively,on the 13th and 17th day after transplantation, with no significant difference (P>0.05).Furthermore, no significant difference in CD25 mRNA expression was found(P>0.05)on the 17th day after transplantation between Antibody group (1.84±0.27) and Control group (1.70±0.23). Conclusion A total of 100 mg of anti-CD25mAb administered in succession by two equal dosages of 50 mg may temporarily decrease the expression of CD4~+CD25~(high) Treg, but won't inhibit activation and proliferation of the neogenetic Treg cells, therefore is harmless for the inducement and maintenance of immune tolerance at the early stage of post transplantation.