异基因骨髓移植小鼠Treg、NK细胞及相关细胞因子与aGVHD的关系  

Relationship of aGVHD with Treg,NK cells as well as their related cytokines in mice with allogeneic bone marrow transplantation

作　　者：爨婷 王剑利[1] 代志明[1] 张卉[1] 张王刚[1] 

机构地区：[1]西安交通大学第二附属医院血液科,陕西西安710004

出　　处：《西安交通大学学报（医学版）》2017年第3期392-396,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金项目资助(No.30800493);陕西省科技攻关项目(No.2012-K13-02-19)~~

摘　　要：目的探讨异基因骨髓移植小鼠体内调节性T细胞(Treg)、NK细胞以及与其功能相关的细胞因子白介素-10(IL-10)、转化生长因子(TGF-β)、穿孔素与急性移植物抗宿主病(aGVHD)的关系。方法建立H-2完全不合的C57BL/6→BALB/c纯种小鼠间异基因骨髓移植后发生aGVHD模型。流式细胞仪检测移植后存活的aGVHD小鼠脾脏CD4+CD25+Treg细胞和NK-1.1+NK细胞的比例;ELISA方法检测环孢素A干预aGVHD小鼠血清IL-10、TGF-β和穿孔素的水平,以正常的C57BL/6小鼠为对照。结果与正常小鼠相比,移植后发生aGVHD小鼠体内Treg细胞比例下降(3.6%vs.1.55%),NK细胞比例上升(3.3%vs.11.5%);环孢素A治疗aGVHD组小鼠,与未干预组相比,血清IL-10水平明显上升[(125.79±0.27)pg/mL vs.(103.09±3.27)pg/mL,P<0.01],TGF-β水平上升但无统计学差异[(252.05±7.84)pg/mL vs.(241.61±15.41)pg/mL,P>0.05],穿孔素水平明显上升[(186.97±4.68)pg/mLvs.(144.35±14.42)pg/mL,P<0.01]。结论 (1)小鼠移植后发生aGVHD与Treg细胞比例下降有关,Treg功能相关的细胞因子IL-10、TGF-β参与环孢素A介导的免疫抑制治疗;(2)NK细胞参与异基因骨髓移植后aGVHD的发生过程,穿孔素的水平上升与抑制aGVHD有关。Objective To investigate the relationship of acute graft versus host disease(aGVHD)and the regulatory T(Treg)cells,NK cells as well as their function-related cytokines such as IL-10,TGF-β,and perforin in mice with allogeneic bone marrow transplantation.Methods H-2 completely mismatched C57BL/6→BALB/c aGVHD mice model was constructed.Flow cytometry analysis was used to detect the proportion of CD4+CD25+Treg cells and NK-1.1+ NK cells in the spleen of aGVHD mice after transplantation.ELISA method was used to detect the serum levels of IL-10,TGF-βand perforin in the aGVHD mice intervened with CSA prophylactic or not.The normal C57BL/6 mice were used as controls.Results Compared with those of normal mice,the proportion of Treg cells in aGVHD mice after transplantation was decreased(mean 3.6% vs.1.55%)and the proportion of NK cells increased(mean 3.3% vs.11.5%).In the aGVHD mice treated with cyclosporine A,serum IL-10 expression level was significantly increased(treated group(125.79±0.27)pg/mL,untreated group [(103.09±3.27)pg/mL,P<0.01)],TGF-βexpression level was increased[(252.05±7.84)pg/mL vs.(241.61±15.41)pg/mL,P>0.05],perforin expression level was significantly increased [(186.97±4.68)pg/mL vs.(144.35±14.42)pg/mL,P<0.01].Conclusion(1) The occurrence of aGVHD is correlated with the decreased number of Treg cells after transplantation in mice.Treg cell function-related cytokines IL-10 and TGF-βare involved in the treatment of aGVHD by cyclosporine A-mediated immunosuppression.(2)NK cells are involved in the occurrence of aGVHD after allogeneic bone marrow transplantation,and the increased level of perforin is related to the inhibition of aGVHD.

关 键 词：调节性T细胞 NK细胞 急性移植物抗宿主病 细胞因子 骨髓移植 

分 类 号：R392.4[医药卫生—免疫学]