Tfh细胞和B细胞在人慢性移植物抗宿主病中的作用及机制  

The Role and Mechanism of Tfh and B Cell in Human Chronic Graft-Versus-Host-Disease

作　　者：吕康康 徐蜜蜜 杜园园 何雪峰[1] 陈峰[1] 马骁[1] 韩悦[1] 吴德沛[1] 刘跃均[1] 徐明珠[1] LYU Kang-Kang;XU Mi-Mi;DU Yuan-Yuan;HE Xue-Feng;CHEN Feng;MA Xiao;HAN Yue;WU De-Pei;LIU Yue-Jun;XU Ming-Zhu(National Clinical Research Center for Hematologic Diseases,Jiangsu Institute of Hematology The First Afiliated Hospital of Soochow University,Institute of Blood and Marrow Transplantation Collaborative Innovation Center of Hematology Sochow University Suzhou 215006,Jiangsu Province,China)

机构地区：[1]国家血液系统疾病临床医学研究中心,江苏省血液研究所,苏州大学附属第一医院,苏州大学造血干细胞移植研究所,血液学协同创新中心,江苏苏州215006

出　　处：《中国实验血液学杂志》2022年第2期593-599,共7页Journal of Experimental Hematology

基　　金：国家科技重大专项课题(2017ZX09304021);国家重点研发计划(2019YFC0840604,2017YFA0104502);江苏省重点研发计划(BE2019798);江苏省医学杰出人才项目(JCRCA2016002);江苏省科教强卫工程-临床医学中心(YXZXA2016002);国家自然科学基金青年基金项目(81500146);江苏省自然科学基金青年基金项目(BK20150356);国家血液系统疾病临床医学研究中心转化研究课题(2020WSC05)。

摘　　要：目的:探寻循环滤泡辅助性T细胞(cTfh)、滤泡外辅助性T细胞和B细胞及其亚群在移植后慢性移植物抗宿主病(cGVHD)中的作用。方法:采集2016-2019年苏州大学附属第一医院64例行异基因造血干细胞移植(al^(lo)-HSCT)合并发生慢性移植物抗宿主病(cGVHD)患者的外周血。采用流式细胞术检测滤泡辅助性T细胞、滤泡外辅助性T细胞和B细胞及其亚群的比例。采用健康供体作为对照。利用Students’T检验法比较两组间各细胞亚群的百分比。结果:与健康供体相比,cGVHD患者外周血中循环滤泡辅助性T细胞(cTfh,CD4^(+)CXCR5^(+))百分比显著降低(0.53%±0.10%vs3.91%±0.60%,P<0.001)。在cGVHD患者和健康供体外周血中均检测到的滤泡外辅助性T细胞(CD44^(hi)CD62L^(lo)PSGL-1^(lo)CD4^(+)),且该细胞在cGVHD患者中表达明显升高(8.86%±0.45%vs 5.38%±0.79%),差异具有统计学意义(P=0.003)。cGVHD患者的B细胞亚群发现显著性改变,两种经历抗原刺激的CD27^(+)B细胞;pre-GC B细胞(CD19^(+)IgD^(+)CD38^(hi)CD27^(+))和浆母细胞/浆细胞(PB/PC,CD19^(+)IgD-CD38^(hi)CD27^(+))的百分比分别为20.91%±2.70%和41.05%±5.00%,较健康供体显著升高(P=0.005,P=0.014)。cGVHD患者未受到抗原刺激的CD27-B细胞则明显降低,其中以初始B细胞(CD19^(+)IgD^(+)CD38^(lo)CD27-)百分比(12.59%±2.63%)降低显著(P=0.025)。cGVHD患者滤泡外辅助性T细胞百分比与PB/PC百分比呈正相关(r=0.43)。结论:较正常人相比,移植后发生cGVHD患者的外周血中cTfh细胞、滤泡外辅助性T细胞和B细胞亚群发生不同程度的变化。Objective:To investigate the role and mechanism of circulating follicular helper T cells(cTfh),extrafollicular helper T cells,B cells and their subsets in chronic graft-versus-host disease(cGVHD)after transplantation.Methods:Peripheral blood of cGVHD 64 patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)at the First Affiliated Hospital of Soochow University from 2016 to 2019 were collected.The percentage of cTfh cells,extrafollicular helper T cells,B cells and subsets were detected by flow cytometry.The healthy donors were detected as control.Percentage of each cell subpopulation between the two groups were compared by the two-tailed Students’T test.Results:The percentage of circulating follicular helper T cells(cTfh,CD4^(+)CXCR5+)was markedly decreased in patients with c GVHD as compared with that in the healthy donors(0.53%±0.10% vs 3.91%±0.60%,P<0.001).The percentage of extrafollicular helper T cells(CD44^(hi)CD62L^(lo)PSGL-1^(lo)CD4^(+)T)of the patients in c GVHD and the healthy donors were 8.86%±0.45%and 5.38%±0.79%(P=0.003).A significant change in B cell subsets was found in the patients with cGVHD.The two types of antigen-stimulate CD27+B cell:the percentages of pre-GC B cells(CD19^(+)IgD^(+)CD38^(hi)CD27^(+))and plasmablast/plasma cells(PB/PC,CD19^(+)Ig D-CD38^(hi)CD27^(+))of patients with c GVHD w ere 20.91%±2.70% and 41.05%±5.00%,respectively,which w ere significantly higher than those in healthy donors(P=0.005,P=0.014).Meanw hile,the percentage of unstimulated CD27-B cells in patients with c GVHD was significantly reduced,especially the naive B cells(CD19^(+)IgD^(+)CD38^(lo)CD27^(-),12.59%±2.63%,P=0.025).There was a positive correlation betw een the percentage of extrafollicular helper T cells and plasmablast/plasma cells(PB/PC)in c GVHD patients(r=0.43).Conclusion:Compared with healthy donor,c Tfh cells,extrafollicular helper T cells and B cell subsets in the peripheral blood of patients with cGVHD after transplantation changed in varying degress.

关 键 词：循环滤泡辅助性T细胞 滤泡外辅助性T细胞 B细胞 异基因造血干细胞移植 慢性移植物抗宿主病 

分 类 号：R457.7[医药卫生—治疗学]