Sandgaard Katrine S, Lewis Joanna, Adams Stuart, Klein Nigel, Callard Robin
aImmunobiology Unit, Institute of Child Health bCoMPLEX, University College London cHaematology, Great Ormond Street Hospital, London, UK.
AIDS. 2014 Jan 14;28(2):209-14. doi: 10.1097/QAD.0000000000000063.
Disease progression and response to antiretroviral therapy (ART) in HIV-infected children is different to that of adults. Immune reconstitution in adults is mainly from memory T cells, whereas in children it occurs predominantly from the naive T-cell pool. It is unclear however what proportion of reconstituted CD4 T cells comes from thymic export and homeostatic proliferation in the periphery. Thymic output is often estimated by measuring T-cell receptor excision circles and markers such as CD31 expressed on recent thymic emigrants but these are confounded by peripheral T-cell division and cannot in themselves be used as quantitative estimates of thymic output.
To compare thymic output in HIV-infected children on ART, HIV-infected children not on ART and uninfected children of different ages.
Combined T-cell receptor excision circle (TREC) and proliferation data are used with a recently described mathematical model to give explicit measures of thymic output.
We found that age-adjusted thymic output is reduced in untreated children with HIV, which increases significantly with length of time on ART.
Our results suggest that a highly active thymus in early childhood may contribute to better immune reconstitution if ART is initiated early in life.
HIV感染儿童的疾病进展及对抗逆转录病毒疗法（ART）的反应与成人不同。成人的免疫重建主要来自记忆T细胞，而儿童的免疫重建主要发生于初始T细胞库。然而，尚不清楚重建的CD4 T细胞中有多大比例来自胸腺输出及外周的稳态增殖。胸腺输出通常通过测量T细胞受体切除环及近期胸腺迁出细胞上表达的标记物（如CD31）来估算，但这些会因外周T细胞分裂而混淆，其本身不能用作胸腺输出的定量估计。
比较接受ART的HIV感染儿童、未接受ART的HIV感染儿童及不同年龄的未感染儿童的胸腺输出。
将T细胞受体切除环（TREC）和增殖数据与最近描述的数学模型相结合，以明确测量胸腺输出。
我们发现，未治疗的HIV感染儿童经年龄调整后的胸腺输出降低，而随着接受ART时间的延长，胸腺输出显著增加。
我们的结果表明，如果在儿童早期开始ART治疗，其活跃的胸腺可能有助于更好的免疫重建。
