免疫活性细胞表达杀伤细胞抑制性受体与造血干细胞移植后移植物抗宿主病的关系(英文)  

Expression of Killer Cell Inhibitor Receptors on Immunocompetent Cells with Relation to Graft-versus-Host Disease after Hematopoietic Stem Cell Transplantation

作　　者：段连宁[1] 陈纯[2] 黄绍良[2] 方建培[2] 魏菁[2] 包蓉[2] 李艳[2] 韩红星[1] 李树浓[2] 

机构地区：[1]解放军空军总医院血液科,北京100036 [2]广州中山大学医学院病理生理教研室和孙逸仙纪念医院小儿内科,广州510089

出　　处：《中国实验血液学杂志》2003年第6期625-632,共8页Journal of Experimental Hematology

基　　金：广东省自然科基金 (编号 0 10 72 2 );广东省卫生厅基金 (编号B2 0 0 10 2 9)资助项目~~

摘　　要：本研究的目的是探讨造血干细胞移植后杀伤细胞抑制性受体 (KIR)CD15 8和CD94与GVHD发生的关系。用流式细胞术检测分析T淋巴细胞和NK细胞表达CD15 8a,CD15 8b和CD94表达状况 ,同时用PCR方法分析供受者HLA Cw配型 ,比较异基因外周血造血干细胞移植 (allo PBSCT)和脐血移植 (UCBT)后该KIR分子变化和HLA Cw相合或错配与GVHD发生的关系。结果表明 :无论是PBSCT或是UCBT ,移植后CD3+CD15 8a+和CD3+CD15 8b+T细胞均增高并以CD8+CD15 8b+细胞升高为主。发生急性与慢性GVHD组CD3+CD15 8b+细胞均呈不同程度升高 ,在急性GVHD病例中升高最明显。急性GVHD期 (即移植早期 )KIR表达增高 ,慢性GVHD阶段 (即移植后期 )KIR呈减低趋势。CD94主要表达于CD3+CD8+T细胞 ,在UCBT或PBSCT后CD94在CD4 +T细胞和CD8+T细胞均明显增高。 5例HLA Cw相合者无 1例发生重症GVHD ;2例HLA Cw不相合病例 ,有 1例发生急重症GVHD ,并死于间质性肺炎 (IP) ,另 1例为AML(M5) ,完全植入 ,无重度GVHD发生 ,但于 5 3天后复发。 4例相关相合移植中 2例无急性GVHD ,而无关相合者 4例均发生不同程度GVHD。结论 :GVHD的发生与KIR表达有一定关系。CD15 8b分子可能是移植后早期T淋巴细胞活化的负调控分子。从T细胞表达KIR来理解GVHD发生机理 。The study was aimed at the exploration of relationship between T cells expressing killer cell inhibitor receptors (KIR, CD158 and CD94) and graft versus host disease (GVHD) after hematopoietic stem cell transplantation. The expression rates of CD158a, CD158b and CD94 on T cells and NK cell were detected by flow cytometry and donor/recipient HLA Cw was analyzed using PCR after peripheral blood stem cell transplantation (PBSCT) and umbilical cord blood transplantation (UCBT). After both PBSCT and UCBT, the rates of CD3 +CD158a + and CD3 +CD158b + T cells increased, especially the rate of CD8 +CD158b + T cells. In both acute and chronic GVHD groups, the rate of CD3 +CD158b + T cells increased, especially in acute GVHD. The CD94 mainly expressed on CD3 +CD8 +T cells. The percen tage of the expression of CD94 on CD4 + and CD8 + cells after UCBT and PBSCT increased significantly. The expression of KIR in GVHD (early stage of transplantation) increased but the expression of KIR in chronic GVHD (advanced stage of transplantation) decreased. Five patients who HLA Cw matched had no severe GVHD. In four patients who underwent allo PBSCT and UCBT from related HLA matched donors, only 2 patients had no aGVHD. Four patients underwent transplantation from unrelated HLA matched donors had GVHD. These observations suggested that there is some relationship between GVHD and KIR expression on T cells. CD158b might be an inhibitory molecule of T cell activated at early stage after transplantation. Understanding the mechanism of GVHD with the expression of KIR on T cells, especially those binding the HLA Cw might shed light on the establishment of the specific immunotolerance for the prevention of GVHD. To pay attention to HLA Cw typing is very important to reduce GVHD and increase GVL effect in related or unrelated HLA matched transplantation.

关 键 词：杀伤细胞抑制性受体 造血干细胞移植 移植物抗宿主病 T淋巴细胞 免疫活性细胞 

分 类 号：R331.2[医药卫生—人体生理学] R392[医药卫生—基础医学]