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(na?ve 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。
滤泡辅助性T细胞、B细胞、HIV感染
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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;Beijing Municipal Administration of Hospitals’ Youth ProgramQML20181702;National Natural Science Foundation of China82072294, 81772165;Beijing Key Laboratory for HIV/AIDS ResearchBZ0089