Analysis of the TCR Repertoire in HIV-Exposed but Uninfected Infants
Analysis of the TCR Repertoire in HIV-Exposed but Uninfected Infants
复制标题
DOI：
10.1038/s41598-019-48434-4
复制
发表时间：
2019-08-16
影响因子：
4.6
通讯作者：
Lohman-Payne, Barbara L.
中科院分区：
文献类型：
--
作者：
Gabriel, Benjamin;Medin, Carey;Lohman-Payne, Barbara L.
母体人类免疫缺陷病毒（HIV）感染已被证明会对暴露于HIV但未感染（HEU）的婴儿产生深远且持久的影响，与未暴露于HIV（HU）的婴儿相比，包括死亡率和发病率增加、免疫变化以及发育迟缓。暴露于HIV或抗逆转录病毒疗法可能影响免疫发育，这可能会增加发病率和死亡率。然而，死亡率和发病率增加与婴儿免疫系统之间的直接联系尚未确定。为了全面了解HEU婴儿与HU婴儿的新生儿T细胞库情况，使用新一代测序技术测定了HEU婴儿脐带血样本中表达的T细胞受体β链（TRB）的多样性，并与来自同一社区的健康（HU）婴儿进行了比较。虽然HU婴儿的TRB库具有广泛的多样性，符合初始T细胞库的预期情况，但HEU婴儿的样本显示出TRB多样性显著降低。这项研究首次证明了HEU和HU脐带血样本之间TRB多样性的差异，并提供了证据表明母体HIV在未发生传播的情况下会影响胎儿的适应性免疫系统。
Maternal human immunodeficiency virus (HIV) infection has been shown to leave profound and lasting impacts on the HIV-exposed uninfected (HEU) infant, including increased mortality and morbidity, immunological changes, and developmental delays compared to their HIV-unexposed (HU) counterparts. Exposure to HIV or antiretroviral therapy may influence immune development, which could increase morbidity and mortality. However, a direct link between the increased mortality and morbidity and the infant's immune system has not been identified. To provide a global picture of the neonatal T cell repertoire in HEU versus HU infants, the diversity of the T cell receptor beta chain (TRB) expressed in cord blood samples from HEU infants was determined using next-generation sequencing and compared to healthy (HU) infants collected from the same community. While the TRB repertoire of HU infants was broadly diverse, in line with the expected idea of a naive T cell repertoire, samples of HEU infants showed a significantly reduced TRB diversity. This study is the first to demonstrate differences in TRB diversity between HEU and HU cord blood samples and provides evidence that maternal HIV, in the absence of transmission, influences the adaptive immune system of the unborn child.