PMN-MDSCs细胞对异基因造血干细胞移植术后患者T淋巴细胞增殖及干扰素-γ分泌的影响  

Effects of polymorphonuclear myeloid-derived suppressor cells on theproliferation and interferon-γ secretion of T lymphocytes in patientsafter allogeneic hematopoietic stem cell transplantation

作　　者：陈璐 倪明 王力 潘成云 亢倩 詹雲 赵鹏 王季石 CHEN Lu;NI Ming;WANG Li;PAN Chengyun;KANG Qian;ZHAN Yun;ZHAO Peng;WANG Jishi(Department of Hematology,the Affiliated Hospital of Guizhou Medical University,Guiyang 550001,Guizhou,China;School of Clinical Medicine,Guizhou Medical University,Guiyang 550004,Guizhou,China;National Clinical Research Center for Hematologic Diseases,the First Affiliated Hospital of Soochow University,Suzhou 215006,Jiangsu,China)

机构地区：[1]贵州医科大学附属医院血液内科,贵州贵阳550001 [2]贵州医科大学临床医学院,贵州贵阳550004 [3]苏州大学附属第一医院国家血液病临床研究中心,江苏苏州215006

出　　处：《贵州医科大学学报》2023年第7期753-758,766,共7页Journal of Guizhou Medical University

基　　金：国家自然科学基金(82160046);国家血液系统疾病临床医学研究中心转化研究课题(2021WWB01);贵州省科学技术基金(Gzwjkj2019-2-011);贵州医科大学附属医院NSFC面上基金培育计划项目(Gyfynsfc-2021-3)。

摘　　要：目的探讨多形核的髓系来源抑制性细胞(PMN-MDSCs)对异基因造血干细胞移植(allo-HSCT)术后患者T淋巴细胞增殖和干扰素-γ(IFN-γ)分泌的影响。方法抽取16例allo-HSCT术后患者第80天及8例健康供者任意时间点空腹全血标本,先采用中性粒细胞分离液分离2组受检者外周血含PMN-MDSCs与T细胞的白细胞、再采用流式分选出患者PMN-MDSCs与T细胞及健康供者PMN-MDSCs;采用瑞氏-姬姆萨(WG)染色观察2组受检者外周血PMN-MDSCs的形态学特征,Annexin V-APC/7-AAD法检测0 h、12 h、24 h及48 h时allo-HSCT术后患者外周血PMN-MDSCs细胞凋亡情况,羧基荧光素琥珀酰亚胺酯(CFSE)染色和荧光酶联免疫斑点(ELISpot)法检测allo-HSCT术后患者外周血PMN-MDSCs对T细胞增殖及IFN-γ表达的影响。结果allo-HSCT术后患者PMN-MDSCs多呈不成熟粒细胞表型,健康供者PMN-MDSCs呈成熟粒细胞表型,且患者PMN-MDSCs于48 h时大部分仍处于存活状态;CFSE和ELISpot实验表明allo-HSCT术后患者PMN-MDSCs可抑制其T淋巴细胞的增殖、分裂及胞内IFN-γ的释放。结论PMN-MDSCs可抑制allo-HSCT术后患者T淋巴细胞的增殖及分泌INF-γ。Objective To investigate the effects of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)on the proliferation and secretion of interferon-γ(IFN-γ)of T lymphocytes in patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Fasting whole blood samples were collected from 16 patients on the 80th day after allo-HSCT and 8 healthy donors at any time point.The neutrophil separation solution was adopted to separate the white blood cells containing PMN-MDSCs and T cells in the peripheral blood of the two groups;the flow cytometry was adopted to sort PMN-MDSCs and T cells from patients and PMN-MDSCs from healthy donors;the weigert-Giemsa staining was adopted to observe the morphological characteristics of PMN-MDSCs in the peripheral blood of the two groups;the Annexin V-APC/7-AAD was adopted to detect the apoptosis of PMN-MDSCs in the peripheral blood of patients after allo-HSCT at 0,12,24,and 48 h;Carboxyfluorescein Succinimidyl Ester(CFSE)staining and fluorescent Enzyme-Linked Immunospot(ELISpot)assay were adopted to detect the effects of PMN-MDSCs on T-cell proliferation and IFN-γexpression in the peripheral blood of patients after allo-HSCT.Results Most of the PMN-MDSCs from patients after allo-HSCT were of immature granulocyte phenotype,while those from healthy donors were of mature granulocyte phenotype,and most of the PMN-MDSCs from patients were still alive at 48 hours.CFSE and ELISpot showed that PMN-MDSCs from patients could inhibit the proliferation,division and intracellular IFN-γrelease of T lymphocytes.Conclusions PMN-MDSCs can inhibit the proliferation and INF-γsecretion of T lymphocytes in patients after allo-HSCT.

关 键 词：T淋巴细胞 细胞增殖 干扰素-Γ 多形核的髓系来源抑制性细胞 免疫抑制 

分 类 号：R551.2[医药卫生—血液循环系统疾病]