PDF(Pubmed)
Abstract：
Introduction: Infant HIV-1-infection is associated with high morbidity and mortality if antiretroviral treatment (ART) is not initiated promptly. We characterized development of circulating T follicular helper cells (cTfh) and their relationship to naïve/memory B cell subsets in a cohort of neonates initiating ART within the first week of life. Methods: Infants were diagnosed within 48 hours of birth and started ART as soon as possible. The frequency and phenotype of cTfh and B cells were analyzed at enrollment (birth -19 days) and at 4, 12, and 72 weeks of age in blood of 27 HIV-1-intrauterine-infected and 25 HIV-1 exposed uninfected (HEU) infants as part of a study in Johannesburg, South Africa. cTfh cells were divided into Tfh1, Tfh2, and Tfh17 subsets. B cell phenotypes were defined as naïve, resting memory, activated memory and tissue-like memory cells. Results: HIV-1-infected infants had higher frequencies of cTfh cells than HEU infants up to 12 weeks of age and these cTfh cells were polarized toward the Tfh1 subset. Higher frequencies of Tfh1 and lower frequencies of Tfh2 and Tfh17 correlated with lower CD4+ T cell percentages. Lower frequencies of resting memory, with corresponding higher frequencies of activated memory B cells, were observed with HIV-1 infection. Importantly, dysregulations in B cell, but not cTfh cell, subsets were normalized by 72 weeks. Conclusion: Very early ART initiation in HIV-1-infected infants normalizes B cell subsets but does not fully normalize perturbations in cTfh cell subsets which remain Tfh1 polarized at 72 weeks. It remains to be determined if very early ART improves vaccine antibody responses despite the cTfh and B cell perturbations observed over the time course of this study.
摘要：
简介：如果不及时启动抗逆转录病毒治疗（ART），婴儿HIV-1感染与高发病率和高死亡率相关。我们描述了循环T滤泡辅助细胞（cTfh）的发展及其与初始/记忆B细胞亚群的关系，这些新生儿在生命的第一周内启动ART。方法：婴儿在出生48小时内确诊，并尽快开始ART。作为约翰内斯堡一项研究的一部分，分析了27名HIV-1宫内感染和25名HIV-1暴露未感染（HEU）婴儿的入组时（出生-19天）和4、12和72周龄时cTfh和B细胞的频率和表型，南非。将cTfh细胞分为Tfh1、Tfh2和Tfh17亚群。B细胞表型被定义为幼稚，休息记忆,激活的记忆和组织样记忆细胞。结果：HIV-1感染的婴儿cTfh细胞的频率高于12周龄的HEU婴儿，并且这些cTfh细胞向Tfh1亚群极化。较高的Tfh1频率和较低的Tfh2和Tfh17频率与较低的CD4+T细胞百分比相关。静息记忆的频率较低，激活的记忆B细胞的频率相应较高，观察到HIV-1感染。重要的是,B细胞失调，但不是cTfh细胞，亚群在72周时恢复正常。结论：HIV-1感染婴儿的早期ART启动可使B细胞亚群正常化，但不能完全使cTfh细胞亚群的扰动正常化，这些细胞亚群在72周时仍保持Tfh1极化。尽管在该研究的时间过程中观察到cTfh和B细胞扰动,但仍需要确定非常早期的ART是否改善疫苗抗体应答。
