供者调控T细胞对异基因造血干细胞移植后造血与免疫重建、移植物抗宿主病发生及生存的影响  

Effect of donor CD4^+CD25^+ regulatory T cells on hematopoietic and immune reconstitution,GVHD and disease-free survival after allogeneic hematopoietic stem cell transplantation

作　　者：杨凯[1] 范志平[1] 刘启发[1] 张钰[1] 

机构地区：[1]南方医科大学南方医院血液科,广东广州510515

出　　处：《南方医科大学学报》2008年第4期537-541,共5页Journal of Southern Medical University

基　　金：广东省自然科学基金(7005160)~~

摘　　要：目的研究接受不同数量供者CD4+CD25+调控T细胞(TReg)移植对异基因造血干细胞移植(allo-HSCT)患者移植物抗宿主病(GVHD)的发生和造血与免疫重建的影响。方法对30例接受allo-HSCT患者采用流式细胞仪测定移植物中的TReg值和移植后患者不同时间点外周血T淋巴细胞亚群及TReg。按移植供者TReg绝对数是否大于或等于10.0×106/kg为标准分为高TReg移植组和低TReg移植组,比较两组患者移植后造血与免疫重建、TReg重建、GVHD发生及无病生存率有无差异。结果高TReg组的白细胞(WBC)和血小板(PLT)重建时间分别为+(8.62±2.29)d和+(12.69±5.74)d,低TReg组分别为+(8.88±2.71)d和+(15.18±6.71)d(P值分别为0.778和0.613),两组间WBC和PLT重建时间无显著性差异。高TReg组患者移植后+15dCD4+CD3+、CD45RO+CD4+T细胞重建,+30dCD3+、CD4+CD3+T细胞重建明显快于低TReg组患者(P值分别为0.039、0.024、0.014、0.020)。高TReg组患者移植后+15dCD4+CD25+TReg重建,+180d与低TReg组相比明显加快(P值分别为0.013、0.005)。高TReg组和低TReg组患者急性GVHD发生率分别为61.54%(8/13)和94.12%(16/17),两组统计有显著性差异(P=0.027),移植的供者TReg数与急性GVHD的发生程度呈负相关(rs=-0.393,P=0.032)。高与低TReg组无病生存率分别为(60.40±16.10)%和(72.00±12.00)%,无显著性差异(P=0.818)。结论供者TReg能促进allo-HSCT后免疫重建及CD4+CD25+TReg重建,降低移植后急性GVHD的发生率。Objective To observe the effect of donor CD4＋CD25＋ regulatory T cells （TReg） on hematopoietic reconstitution, immune reconstitutuion and graft-versus-host disease （GVHD） following allogeneic hematopoietic stem cell transplantation （alIo-HSCT）. Methods Thirty patients were divided into high TReg group （TReg I〉 10.0×10^6 cells/kg, n=13） and low TReg group （TReg〈10.0×10^6cells/kg, n=17） according to the number of TReg in the grafts. Flow cytometry （FCM） was used to detect the TReg percentage in the grafts and recipients peripheral blood T lymphocyte subsets and TReg at different time points after alIo-HSCT. The hematopoietic reconstitution, immune reconstitution, TReg reconstitution, incidence of GVHD and disease-free survival were compared between the two groups. Results The high and low TReg groups showed similar WBC reconstitution time （＋8.62±2.29 vs ＋8.88±2.71 days, P=-0.778） and platelet reconstitution time （＋12.69±5.74 vs ＋15.18±6.71 days, P=-0.613）. In high TReg group, the reconstitutions ofCD4＋CD3＋ and CD45RO＋CD4＋ T cells on day 15 and CD3＋ and CD4＋CD3＋ T cells on day 30 were significantly accelerated in comparison with those of the low TReg group （with P values of 0.039, 0.024, 0.014, 0.020, respectively）. TReg reconstitution 15 and 180 days following the surgery was significantly faster in high TReg group than in low TReg group （P=-0.013, 0.005, respectively）. The incidence of acute GVHD in high TReg group （61.54%） was obviously lower than that in low TReg group （94.12%, P=0.027）. A negative correlation was found between the number of infused donor TReg and the severity of acute GVHD （rs=-0.393, P=0.032）. The one-year disease-free survival rates of the high and low TReg groups were （60.40± 16.10）% and （72.00± 12.00）%, respectively, showing no significant difference between the two groups （P=0.818）. Conclusion Donor TReg may promote immunological reconstitution and TReg reconstitution, and decrease the inci

关 键 词：调控T细胞 异基因造血干细胞移植 造血与免疫重建:移植物抗宿主病 

分 类 号：R457.7[医药卫生—治疗学]