HIV暴露和母亲结核分枝杆菌感染对婴儿卡介苗接种免疫反应的影响。
The impact of HIV exposure and maternal Mycobacterium tuberculosis infection on infant immune responses to bacille Calmette-Guérin vaccination.
作者信息
Jones Christine E, Hesseling Anneke C, Tena-Coki Nontobeko G, Scriba Thomas J, Chegou Novel N, Kidd Martin, Wilkinson Robert J, Kampmann Beate
机构信息
aAcademic Department of Pediatrics, Imperial College London, London, UK bInstitute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa cPaediatric Infectious Diseases Research Group, St George's, University of London, London, UK dDesmond Tutu TB Centre, Department of Pediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Stellenbosch eSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town fDST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University gDivision of Statistics and Actuarial Sciences, Faculty of Science, University of Stellenbosch, Stellenbosch, South Africa hMRC National Institute for Medical Research, Mill Hill, London, UK iClinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa jDivision of Medicine, Imperial College London, London, UK kVaccinology Theme, Medical Research Council Unit, Banjul, The Gambia.
出版信息
AIDS. 2015 Jan 14;29(2):155-65. doi: 10.1097/QAD.0000000000000536.
OBJECTIVE
The objective of this study is to assess the effect of maternal HIV and Mycobacterium tuberculosis (Mtb) infection on cellular responses to bacille Calmette-Guérin (BCG) immunization.
DESIGN
A mother-infant cohort study.
METHODS
Samples were collected from mother-infant pairs at delivery. Infants were BCG-vaccinated at 6 weeks of age and a repeat blood sample was collected from infants at 16 weeks of age. BCG-specific T-cell proliferation and intracellular cytokine expression were measured by flow cytometry. Secreted cytokines and chemokines in cell culture supernatants were analysed using a Multiplex assay.
RESULTS
One hundred and nine (47 HIV-exposed and 62 HIV-unexposed) mother-infants pairs were recruited after delivery and followed longitudinally. At birth, proportions of mycobacteria-specific proliferating T cells were not associated with either in-utero HIV exposure or maternal Mtb sensitization. However, in-utero HIV exposure affected infant-specific T-cell subsets [tumour necrosis factor-alpha (TNF-α) single positive proliferating CD4⁺ T cells and interferon-gamma (IFN-γ), TNF-α dual-positive CD4⁺ T cells]. Levels of TNF-α protein in cell culture supernatants were also significantly higher in HIV-exposed infants born to Mtb-sensitized mothers. In the presence of maternal Mtb sensitization, frequencies of maternal and newborn BCG-specific proliferating CD4⁺ T cells were positively correlated. Following BCG vaccination, there was no demonstrable effect of HIV exposure or maternal Mtb infection on infant BCG-specific T-cell proliferative responses or concentrations of secreted cytokines and chemokines.
CONCLUSION
Effects of maternal HIV and Mtb infection on infant immune profiles at birth are transient only, and HIV-exposed, noninfected infants have the same potential to respond to and be protected by BCG vaccination as HIV-unexposed infants.
目的
本研究的目的是评估母亲感染人类免疫缺陷病毒（HIV）和结核分枝杆菌（Mtb）对卡介苗（BCG）免疫细胞反应的影响。
设计
母婴队列研究。
方法
在分娩时从母婴对中采集样本。婴儿在6周龄时接种卡介苗，并在16周龄时从婴儿采集重复血样。通过流式细胞术测量卡介苗特异性T细胞增殖和细胞内细胞因子表达。使用多重分析法分析细胞培养上清液中分泌的细胞因子和趋化因子。
结果
分娩后招募了109对母婴对（47对暴露于HIV和62对未暴露于HIV）并进行纵向随访。出生时，分枝杆菌特异性增殖T细胞的比例与宫内HIV暴露或母亲Mtb致敏均无关。然而，宫内HIV暴露影响婴儿特异性T细胞亚群[肿瘤坏死因子-α（TNF-α）单阳性增殖CD4⁺T细胞和干扰素-γ（IFN-γ）、TNF-α双阳性CD4⁺T细胞]。在对Mtb致敏的母亲所生的暴露于HIV的婴儿中，细胞培养上清液中TNF-α蛋白水平也显著更高。在母亲Mtb致敏的情况下，母亲和新生儿卡介苗特异性增殖CD4⁺T细胞的频率呈正相关。接种卡介苗后，HIV暴露或母亲Mtb感染对婴儿卡介苗特异性T细胞增殖反应或分泌的细胞因子和趋化因子浓度没有明显影响。
结论
母亲HIV和Mtb感染对出生时婴儿免疫特征的影响仅是短暂的，暴露于HIV但未感染的婴儿与未暴露于HIV的婴儿对卡介苗接种产生反应并获得保护的潜力相同。
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