HIV感染者外周血Tfh细胞与B细胞异常分化相关性分析  

Correlation between circulating T follicular helper cells and abnormal shift in B cell differentiation during HIV infection

作　　者：陆小凡[1] 张欣[1] 夏欢[1] 李珍[1] 计云霞[1] 吴昊[1] 张彤[1] 粟斌[1] Lu Xiaofan;Zhang Xin;Xia Huan;Li Zhen;Ji Yunxia;Wu Hao;Zhang Tong;Su Bin(Beijing Key Laboratory for HIV/AIDS Research,Clinical and Research Center for Infectious Diseases,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京佑安医院,感染性疾病临床研究中心,艾滋病研究北京市重点实验室,北京100069

出　　处：《中华实验和临床病毒学杂志》2022年第1期40-45,共6页Chinese Journal of Experimental and Clinical Virology

基　　金：北京市医管中心人才培养"青苗"计划(QML20181702);国家自然科学基金项目(82072294,81772165);艾滋病研究北京市重点实验室(BZ0089)。

摘　　要：目的探讨HIV感染急性期(acute HIV infection,AHI)和慢性期(chronic HIV infection,CHI)外周血滤泡辅助性T细胞(circulating T follicular helper cell,cTfh)的动力学变化及对B细胞分化的影响。方法从北京佑安医院男男性行为高危筛查队列中筛选HIV感染者和HIV阴性的健康对照者(healthy controller,HC)。采用流式分析方法,分别检测AHI、CHI和HC组cTfh细胞和B细胞亚群的比例和数量并进行比较分析。结果与HC相比,cTfh细胞比例在AHI显著升高并持续至CHI,但AHI和CHI无显著差异(AHI vs HC:2.09±1.48 vs 0.26±0.38,t=5.25,P<0.001;CHI vs HC:2.26±1.35 vs 0.26±0.38,t=6.25,P<0.001;AHI vs CHI:2.09±1.48 vs 2.26±1.35,t=0.40,P=0.449)。B细胞各亚群中,活化记忆B细胞(activated memory,AM)、组织样记忆B细胞(tissue-like memory,TLM)和浆母细胞(plasmablast,PB)的比例在AHI和CHI均显著升高[AM(AHI vs HC:3.59±1.77 vs 0.83±0.44,t=6.65,P<0.001;CHI vs HC:3.99±2.49 vs 0.83±0.44,t=5.46,P<0.001);TLM(AHI vs HC:11.05±4.96 vs 1.30±0.93,t=8.45,P<0.001;CHI vs HC:13.91±6.59 vs 1.30±0.93,t=8.28,P<0.001);PB(AHI vs HC:3.01±2.50 vs 0.43±0.26,t=4.47,P<0.001;CHI vs HC:1.88±1.57 vs 0.43±0.26,t=3.97,P<0.001)],静息记忆B细胞(resting memory,RM)和初始成熟B细胞(naïve mature,NM)在AHI和CHI较HC显著下降[RM(AHI vs HC:20.06±9.74 vs 25.43±10.91,t=1.70,P=0.040;CHI vs HC:15.70±8.47 vs 25.43±10.91,t=3.29,P=0.003);NM(AHI vs HC:55.71±13.88 vs 66.26±11.71,t=2.90,P=0.004;CHI vs HC:58.33±14.47 vs 66.26±11.71,t=1.94,P=0.006)]。相关性分析发现,cTfh细胞比例在AHI与AM(r=0.67,P<0.001)、经典记忆B细胞(classical memory,CM)(r=0.59,P=0.001)、RM(r=0.47,P=0.010)和PB(r=0.65,P<0.001)正相关性,与NM负相关(r=-0.55,P=0.003)。CHI除与PB正相关外(r=0.56,P=0.003),未发现cTfh细胞比例与其他B细胞亚群有相关性。结论AHI引起cTfh细胞扩增,由此可能导致B细胞异常分化,从而影响抗体的产生。Objective To understand the dynamics of circulating Tfh(cTfh)and B cells,and their relationship in individuals with acute(AHI)and chronic HIV infection(CHI).Methods HIV infected subjects and HIV negative healthy controllers(HC)were enrolled from the men who have sex with men(MSM)high-risk cohort at Beijing Youan hospital.Multicolor flow cytometry was used for the frequency and absolute number analysis of cTfh cell and B-cell subsets with AHI,CHI,and HC.Results Compared to HC,AHI resulted in an increase in cTfh cell levels and persisted into CHI,however,there was no significant difference between AHI and CHI(AHI vs HC:2.09±1.48 vs 0.26±0.38,t=5.25,P<0.001;CHI vs HC:2.26±1.35 vs 0.26±0.38,t=6.25,P<0.001;AHI vs CHI:2.09±1.48 vs 2.26±1.35,t=0.40,P=0.449).Among B cell subsets,activated memory(AM),tissue-like memory(TLM),and plasmablast(PB)cell levels increased[AM(AHI vs HC:3.59±1.77 vs 0.83±0.44,t=6.65,P<0.001;CHI vs HC:3.99±2.49 vs 0.83±0.44,t=5.46,P<0.001);TLM(AHI vs HC:11.05±4.96 vs 1.30±0.93,t=8.45,P<0.001;CHI vs HC:13.91±6.59 vs 1.30±0.93,t=8.28,P<0.001);PB(AHI vs HC:3.01±2.50 vs 0.43±0.26,t=4.47,P<0.001;CHI vs HC:1.88±1.57 vs 0.43±0.26,t=3.97,P<0.001)],whereas resting memory(RM)and naïve mature(NM)cell levels decreased in both AHI and CHI[RM(AHI vs HC:20.06±9.74 vs 25.43±10.91,t=1.70,P=0.040;CHI vs HC:15.70±8.47 vs 25.43±10.91,t=3.29,P=0.003);NM(AHI vs HC:55.71±13.88 vs 66.26±11.71,t=2.90,P=0.004;CHI vs HC:58.33±14.47 vs 66.26±11.71,t=1.94,P=0.006)].The levels of cTfh cells were positively correlated with those of AM(r=0.67,P<0.001),classical memory(CM)(r=0.59,P=0.001),RM(r=0.47,P=0.010),and PB(r=0.65,P<0.001),and negatively correlated with those of NM B cells in AHI(r=-0.55,P=0.003).However,cTfh cells did not show any relationship with B cell subsets except for the positive correlation with PB(r=0.56,P=0.003)in CHI.Conclusions HIV infection drives the expansion of cTfh cells,which may in turn leads to perturbations of B cell differentiation during AHI stage.

关 键 词：滤泡辅助性T细胞 B细胞 HIV感染 

分 类 号：R512.91[医药卫生—内科学]