Garcia-Knight Miguel A, Nduati Eunice, Hassan Amin S, Gambo Faith, Odera Dennis, Etyang Timothy J, Hajj Nassim J, Berkley James Alexander, Urban Britta C, Rowland-Jones Sarah L
NDM Research Building, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
KEMRI-Wellcome Trust Research Program, Centre for Geographical Medicine Research, Kilifi, Kenya.
PLoS One. 2015 Nov 16;10(11):e0143043. doi: 10.1371/journal.pone.0143043. eCollection 2015.
Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy and T-cell immunity in this vulnerable population is warranted.
成功实施预防母婴传播艾滋病毒策略，导致艾滋病毒暴露未感染（HEU）婴儿数量增加。与未暴露于艾滋病毒（HU）的婴儿相比，HEU婴儿的发病率和死亡率更高。许多因素可能导致HEU婴儿健康状况不佳，包括免疫改变。本研究评估了HEU婴儿的T细胞表型和功能，重点是对疫苗接种的记忆性Th1反应。我们对肯尼亚艾滋病毒暴露（n = 42）和HU（n = 28）婴儿在3个月和12个月大时的横断面选择参数进行了比较。我们通过流式细胞术测量了体外活化的和总体记忆性CD4和CD8 T细胞以及调节性T细胞。此外，我们测量了对卡介苗和破伤风类毒素疫苗抗原的抗原特异性T细胞反应的强度、质量和记忆表型，以及用葡萄球菌肠毒素B进行多克隆刺激后T细胞反应的强度和质量。最后，在HEU婴儿中评估了母体疾病标志物对所测量免疫参数的影响。尽管在体外T细胞亚群中检测到的扰动较少，但在HEU婴儿中，母体艾滋病毒病毒载量与12个月时的CD8 T细胞免疫激活呈正相关。相反，我们观察到对疫苗抗原的IL-2和TNF-α反应的强度和多功能性存在年龄依赖性差异，特别是在Th1细胞中。这些变化反映了多克隆刺激后的情况，在3个月时，HEU婴儿的细胞因子反应高于HU婴儿，而在12个月时，HEU婴儿的细胞因子反应始终低于HU婴儿。最后，在3个月和12个月时观察到HEU婴儿对疫苗抗原的效应记忆性Th1反应降低，仅在3个月时观察到对结核分枝杆菌抗原的中央记忆性Th1反应较高。有必要对这一脆弱人群的疫苗效力和T细胞免疫进行长期监测。
