Premature aging and immune senescence in HIV-infected children.
Premature aging and immune senescence in HIV-infected children.
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DOI：
10.1097/qad.0000000000001093
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发表时间：
2016-06-01
期刊：
影响因子：
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通讯作者：
De Rossi A
中科院分区：
文献类型：
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作者：
Gianesin K;Noguera-Julian A;Zanchetta M;Del Bianco P;Petrara MR;Freguja R;Rampon O;Fortuny C;Camós M;Mozzo E;Giaquinto C;De Rossi A
一些证据表明，感染艾滋病毒的成年人会过早衰老。艾滋病毒和抗逆转录病毒治疗（ART）暴露对艾滋病毒感染儿童衰老过程的影响可能更有害，因为他们的免疫系统从出生时就与艾滋病毒共同进化。对71例HIV感染（HIV+）、65例HIV暴露-未感染（HEU）和56例HIV未暴露-未感染（HUU）儿童进行了0-5岁的生物学衰老和免疫衰老研究。实时荧光定量PCR检测外周血端粒长度和t细胞受体重排切除环水平。流式细胞术分析CD4+和CD8+细胞的分化、衰老和激活/衰竭标志物。HIV+儿童的端粒长度明显短于HEU和HUU儿童（总体而言，经年龄调整后P < 0.001）；未接受ART治疗的HIV+儿童（42%）端粒长度比接受ART治疗的儿童短（经年龄调整后P = 0.003）。HIV+组t细胞受体重排切除环水平和CD8+最近胸腺迁移细胞（CD45RA+CD31+）水平显著低于对照组（P = 0.025和P = 0.005）。HIV+组中衰老（CD28−CD57+）、活化（CD38+HLA-DR+）和耗竭（PD1+） CD8+细胞的百分比显著高于HEU和HUU组（P分别为0.004、P < 0.001和P < 0.001）。在CD4+细胞亚群中，衰老细胞的百分比在HIV+和对照组之间没有差异，但前者的程序性细胞死亡受体-1表达上调。感染艾滋病毒的儿童表现出过早的生物衰老和加速的免疫衰老，这尤其影响CD8+细胞亚群。艾滋病毒感染本身似乎影响衰老过程，而不是为了预防或治疗而接受抗逆转录病毒治疗。
Supplemental Digital Content is available in the text Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV. Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0–5 years, were studied for biological aging and immune senescence. Telomere length and T-cell receptor rearrangement excision circle levels were quantified in peripheral blood cells by real-time PCR. CD4+ and CD8+ cells were analysed for differentiation, senescence, and activation/exhaustion markers by flow cytometry. Telomere lengths were significantly shorter in HIV+ than in HEU and HUU children (overall, P < 0.001 adjusted for age); HIV+ ART-naive (42%) children had shorter telomere length compared with children on ART (P = 0.003 adjusted for age). T-cell receptor rearrangement excision circle levels and CD8+ recent thymic emigrant cells (CD45RA+CD31+) were significantly lower in the HIV+ than in control groups (overall, P = 0.025 and P = 0.005, respectively). Percentages of senescent (CD28−CD57+), activated (CD38+HLA-DR+), and exhausted (PD1+) CD8+ cells were significantly higher in HIV+ than in HEU and HUU children (P = 0.004, P < 0.001, and P < 0.001, respectively). Within the CD4+ cell subset, the percentage of senescent cells did not differ between HIV+ and controls, but programmed cell death receptor-1 expression was upregulated in the former. HIV-infected children exhibit premature biological aging with accelerated immune senescence, which particularly affects the CD8+ cell subset. HIV infection per se seems to influence the aging process, rather than exposure to ART for prophylaxis or treatment.