Disease Progression in Children With Perinatal Human Immunodeficiency Virus Correlates With Increased PD-1+ CD8 T Cells That Coexpress Multiple Immune Checkpoints.
Disease Progression in Children With Perinatal Human Immunodeficiency Virus Correlates With Increased PD-1+ CD8 T Cells That Coexpress Multiple Immune Checkpoints.
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患有围产期人类免疫缺陷病毒的儿童的疾病进展与共表达多个免疫检查点的 PD-1 CD8 T 细胞增加相关。
DOI：
10.1093/infdis/jiab204
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Khaitan,Alka
中科院分区：
文献类型：
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作者：
Tailor,Janki;Foldi,Julia;Generoso,Matthew;McCarty,Bret;Alankar,Aparna;Kilberg,Max;Mwamzuka,Mussa;Marshed,Fatma;Ahmed,Aabid;Liu,Mengling;Borkowsky,William;Unutmaz,Derya;Khaitan,Alka
背景：PD-1标记耗竭的T细胞，具有较弱的效应功能。成年HIV感染者PD-1+ CD8 T细胞水平升高与HIV疾病进展相关，但PD-1+ CD8 T细胞在围产期HIV患儿中的作用尚不清楚。方法：我们招募了76名肯尼亚围产期艾滋病毒儿童和43名未暴露于艾滋病毒的儿童，并量化了CD8 T细胞上的PD-1水平，它们与免疫检查点（IC） 2B4、CD160和TIM3的共表达，与免疫激活和艾滋病毒疾病进展以及艾滋病毒特异性和非特异性增殖反应相关。结果：PD-1+ CD8 T细胞频率在围产期HIV患儿中升高，并与疾病进展相关。大多数PD-1+ CD8 T细胞共表达额外的ic。ART启动降低PD-1总水平和多个ic的共表达。PD-1+ 2B4+ CD160+ tim3在PD-1+ CD8 T细胞中的频率预测较弱的hiv特异性增殖反应，表明该亚群功能耗尽。结论：围产期HIV患儿具有高PD-1+ CD8 T细胞，这是一个异质群体，差异共表达多个ic。了解ic的复杂相互作用对于指导PD-1导向的儿童HIV缓解和治愈免疫疗法的发展至关重要。
BACKGROUND: PD-1 marks exhausted T cells, with weak effector functions. Adults living with HIV have increased levels of PD-1+ CD8 T cells that correlate with HIV disease progression, yet little is known about the role of PD-1+ CD8 T cells in children with perinatal HIV.METHODS: We enrolled 76 Kenyan children with perinatal HIV and 43 children who were HIV unexposed and quantified PD-1 levels on CD8 T cells, their coexpression with immune checkpoints (IC) 2B4, CD160 and TIM3, correlates with immune activation and HIV disease progression and HIV-specific and non-specific proliferative responses.RESULTS: PD-1+ CD8 T cell frequencies are elevated in children with perinatal HIV and associated with disease progression. The majority of PD-1+ CD8 T cells coexpress additional ICs. ART initiation lowers total PD-1 levels and coexpression of multiple ICs. The frequency of PD-1+ 2B4+ CD160+ TIM3-in PD-1+ CD8 T cells, predicts weaker HIV-specific proliferative responses, suggesting this subset is functionally exhausted.CONCLUSION: Children with perinatal HIV have high PD-1+ CD8 T cells that are a heterogeneous population differentially coexpressing multiple ICs. Understanding the complex interplay of ICs is essential to guide the development of PD-1 directed immunotherapies for pediatric HIV remission and cure.