Disrupted memory T cell expansion in HIV-exposed uninfected infants is preceded by premature skewing of T cell receptor clonality.
Disrupted memory T cell expansion in HIV-exposed uninfected infants is preceded by premature skewing of T cell receptor clonality.
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在暴露于 HIV 的未感染婴儿中，记忆性 T 细胞增殖受到破坏，随后 T 细胞受体克隆性就会过早发生偏差。
DOI：
10.1101/2023.05.19.540713
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Gray,CliveM
中科院分区：
文献类型：
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作者：
Dzanibe,Sonwabile;Wilk,AaronJ;Canny,Susan;Ranganath,Thanmayi;Alinde,Berenice;Rubelt,Florian;Huang,Huang;Davis,MarkM;Holmes,Susan;Jaspan,HeatherB;Blish,CatherineA;Gray,CliveM
虽然预防艾滋病毒垂直传播非常成功，但与艾滋病毒未暴露和未感染婴儿（iHUU）相比，越来越多的艾滋病毒暴露未感染婴儿（iHEU）的感染风险增加。iHEU和iHUU之间的免疫发育差异仍然知之甚少，在这里，我们提出了一个纵向多模式分析婴儿免疫个体发育，突出了艾滋病毒/抗逆转录病毒药物暴露的影响。使用质谱细胞术，我们显示了iHEU和iHUU之间NK细胞群体和T细胞记忆分化的出现的改变和差异。出生时观察到的特异性NK细胞也可预测无细胞百日咳和轮状病毒疫苗诱导的IgG和伊加反应，分别在3个月和9个月的生活。在T细胞记忆扩展之前，iHEU中T细胞受体Vβ克隆型多样性显著且持续降低。我们的研究结果表明，艾滋病毒/抗逆转录病毒药物暴露破坏了先天免疫和自出生以来的适应性免疫，这可能是相对易受感染的基础。
While preventing vertical HIV transmission has been very successful, the increasing number of HIV-exposed uninfected infants (iHEU) experience an elevated risk to infections compared to HIV-unexposed and uninfected infants (iHUU). Immune developmental differences between iHEU and iHUU remains poorly understood and here we present a longitudinal multimodal analysis of infant immune ontogeny that highlights the impact of HIV/ARV exposure. Using mass cytometry, we show alterations and differences in the emergence of NK cell populations and T cell memory differentiation between iHEU and iHUU. Specific NK cells observed at birth were also predictive of acellular pertussis and rotavirus vaccine-induced IgG and IgA responses, respectively, at 3 and 9 months of life. T cell receptor Vβ clonotypic diversity was significantly and persistently lower in iHEU preceding the expansion of T cell memory. Our findings show that HIV/ARV exposure disrupts innate and adaptive immunity from birth which may underlie relative vulnerability to infections.