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重组人粒细胞集落刺激因子对健康供者免疫细胞的影响及其应用安全性*

来源:中国造血干细胞捐献者资料库北京管理中心 时间:2015-11-11

徐娟  宋伟  金辉  孙雪静  苏力 李涛 冀冰心 张晨伟  (①首都医科大学宣武医院血液科, 北京 100053;②中国造血干细胞捐献者资料库北京管理中心,北京 100088)

 

摘要  

目的:观察重组人粒细胞集落刺激因子(rhG-CSF)在动员造血干细胞时对健康供者外周血T细胞表面活化信号(CD4+CD28+, CD8+CD28+)、活化T细胞(CD4+CD25low)和调节性 T细胞 (CD4+CD25high)的影响及其应用的安全性。

方法:30例造血干细胞健康供者[男19,女11,中位年龄28(14~56)岁 ]皮下注射 rhG-CSF 5μg/( kg·d),连续 4~6d。用药前及停药后第 1天、第 3天及第7天用流式细胞术检测供者外周血 CD4+T细胞和 CD8+T细胞表面CD28表达的相对荧光强度(RFI),以及 CD4+CD25low和 CD4+CD25highT细胞分别在 CD4+T细胞中的百分比;并在用药前及停药后第 1天、第7天及第30天进行外周血白细胞、血小板、肝功能、肾功能以及脾超声检查。

结果:CD4+CD28T细胞和 CD8+CD28T细胞相对荧光强度表达在用药前分别为14.91±6.10和11.10±3.74,停药后第3天分别降至11.93±5.39和8.53±3.74;差异有统计学意义(P=0.034,P=0.033)。CD4+CD25lowT细胞在 CD4+T细胞中百分比,用药前为(21.4±8.87)% ,停药后第3天降至(18.23±5.89)%;差异无统计学意义( P > 0.05)。CD4+CD25highT细胞在CD4+T细胞中百分比,用药前为(4.16±1.62)%,停药后第1天升至 (6.43±2.46)%,差异有统计学意义(P=0.000)。白细胞计数和脾超声检查用药前分别为(5.91±1.02)×109/L和 (33.76±2.76) cm2,停药后第1天分别升至(34.13±8.07)×109/L和(46.85 ± 4.53)cm2;血小板计数用药前为(228.07±73.69)×109/L,停药后第7天降至(158.27±40.69)×109/L,差异均有统计学意义(P均=0.000)。ALT和Cr用药前分别为(28.23±7.69) IU/L和(60.70 ± 15.86)μmol /L,停药后第1天分别为 (27.17 ± 7.23) IU /L和(61.10 ± 16.38) μmol /L,差异均无统计学意义( P均 > 0.05)。

结论:rhG-CSF能减弱CD28的表达,降低 CD4+CD25low和增加 CD4+CD25high在 CD4+T细胞中百分比,停药后第7天恢复至动员前水平 ,对健康供者肝肾功能无不利影响。

关键词   重组人粒细胞集落刺激因子; 健康供者; 活化 T细胞; 调节性 T细胞; 安全性

中图分类号:  R 977     文献标识码:  A     文章编号:  10082 5734 (2007) 52 03112 05

 

Effects of recom binant human granulocyte colony-stimulating factor on immunocytes inhealth donors and its s afety of application

Xu Juan SongWei, Jin Hui, Sun Xuejing,Su Li, Li Tao, JiB ingxin, Zhang Chenwei  (①Department of Hem atology, Xuanwu Hospital of CapitalMedical Univer sity,Beijing 100053, China;② The Data Bank of Chinese Hem atopoietic Stem Cell Donors Beijing Management Center, Beijing 100088, China)
 

ABSTRACT 

Objective:To observe the effects of recombinant human granulocyte colony-stimulating fact or ( rhG-CSF) on peripheral active signal of T cell surface antigen (CD4+CD28+,CD8+CD28+) , activated T cells, and regulatory T cells during mobilizati on of hemat opoietic stem cells and its safety of applicati on in health donors .

Methods:Thirty normal hemat opoietic stem cells donors (19males, 11 females, median age 28 years, range 14~56 years) received rhG-CSF 5μg/kg daily subcutaneously for 4~6 days .Relative fluorescence intensity ( RFI) of CD28 antigen expression on peri pheral CD4+ cells and CD8+cells,the percentage ofCD4+CD25low and CD4+CD25high in CD4+ T cells were measured with a flow cytometry before rhG-CSF administrati on and on day 1,day 3, and day 7 after rhG-CSF discontinuation, respectively . The peri pheralWBC and PLT counts, liver and renal functions, and ultrasonic measurement of spleen were performed on the day1, day 7, and day 30 after rhG-CSF discontinuati on .

Results:Relative fluorescence intensity of CD28 antigen expression on peripheral CD4+cells and CD8+cells was 14.91 ± 6.10 and 11.10 ± 3.74 before rhG-CSF administration, respectively, and decreased to 11.93 ±5.39 and 8.53 ±3.74 on day 3 after rhG-CSF discontinuation,respectively . The differences were statistically significant ( P = 0.034, P=0.033). The percentage of CD4+CD25low T cells in CD4+cells was (21.4 ±8.87)% before rhG-CSF administration, and decreased to (18.23 ±5.89) % on day 3 after rhG-CSF discontinuation. The difference was no statistically significant( P > 0.05) . The percentage of CD4+CD25high T cells in CD4+ T cells was (4.16 ± 1.62) % before rhG-CSF administration and increased to (6.43 ± 2.46)% on day 1 after rhG-CSF discontinuation . The difference was statistically significant (P = 0.000). The WBC count and ultras onic measurement of sp een were (5.91 ± 1.02) × 109/L and (33.76 ± 2.76) cm2 before rhG-CSF administration, respectively, and increased to ( 34.13 ±8.07) ×109/L and (46.85 ±4153) cm2on day 1 after rhG-CSF discontinuation;the PLT conut were (228.07 ± 73.69) × 109/L before rhG-CSF administration,and decreased to (158.27 ± 40.69) × 109/L on day 7 after rhG-CSF discontinuation . The differenceswere statistically significant ( al

 

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