In-utero exposure to maternal HIV infection alters T-cell immune responses to vaccination in HIV-uninfected infants.
In-utero exposure to maternal HIV infection alters T-cell immune responses to vaccination in HIV-uninfected infants.
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DOI：
10.1097/qad.0000000000000292
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发表时间：
2014-06-19
期刊：
影响因子：
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通讯作者：
Jaspan HB
中科院分区：
文献类型：
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作者：
Kidzeru EB;Hesseling AC;Passmore JA;Myer L;Gamieldien H;Tchakoute CT;Gray CM;Sodora DL;Jaspan HB
在撒哈拉以南非洲，感染艾滋病毒的未感染(HEU)婴儿的发病率和死亡率高于未感染艾滋病毒的婴儿。为了评估免疫功能障碍是否导致HEU婴儿的这种脆弱性，我们进行了一项纵向的观察性队列研究，以评估婴儿疫苗(牛分枝杆菌卡介苗和无细胞百日咳)和葡萄球菌肠毒素B(SEB)的T细胞免疫反应。总共从开普敦的卡耶利沙招募了46名HEU和46名未接触艾滋病毒的婴儿。分别在6周龄和14周龄用抗原刺激小鼠全血，检测疫苗特异性T细胞增殖(Ki67表达)和细胞内4种细胞因子[干扰素-γ、白介素2、白介素13和白介素17]的表达。高血压性尿毒症患儿14周时表现出卡介苗特异性T细胞增殖反应增强(P=0.041和0.002)。即使在调整了出生体重、喂养方式和胎龄后，这些反应也显著增加。与卡介苗相似，尽管百日咳特异性T细胞在两组间的增殖相似，但SEB刺激可明显促进CD_4~+和CD_8~+T细胞的增殖(分别为P=0.004和0.002)。在HEU婴儿中，母亲的CD4+细胞计数和产前抗逆转录病毒暴露的时间长短对T细胞对卡介苗或SEB的增殖没有影响。对卡介苗、百日咳杆菌和SEB刺激的反应中，HIV暴露显著降低了可测量的细胞因子的多功能性。这些数据首次表明，在调整混杂因素后，在子宫内暴露于艾滋病毒与婴儿对疫苗和非特异性抗原的CD4+和CD8+T细胞免疫反应的显著变化有关。
In sub-Saharan Africa, HIV-exposed uninfected (HEU) infants have higher morbidity and mortality than HIV-unexposed infants. To evaluate whether immune dysfunction contributes to this vulnerability of HEU infants, we conducted a longitudinal, observational cohort study to assess T-cell immune responses to infant vaccines (Mycobacterium bovis BCG and acellular pertussis) and staphylococcal enterotoxin B (SEB). In total, 46 HEU and 46 HIV-unexposed infants were recruited from Khayelitsha, Cape Town. Vaccine-specific T-cell proliferation (Ki67 expression) and intracellular expression of four cytokines [interferon-γ, interleukin (IL)-2, IL-13 and IL-17] were measured after whole blood stimulation with antigens at 6 and 14 weeks of age. HEU infants demonstrated elevated BCG-specific CD4+ and CD8+ T-cell proliferative responses at 14 weeks (P = 0.041 and 0.002, respectively). These responses were significantly increased even after adjusting for birth weight, feeding mode and gestational age. Similar to BCG, increased CD4+ and CD8+ T-cell proliferation was evident in response to SEB stimulation (P = 0.004 and 0.002, respectively), although pertussis-specific T cells proliferated comparably between the two groups. Within HEU infants, maternal CD4+ cell count and length of antenatal antiretroviral exposure had no effect on T-cell proliferation to BCG or SEB. HIV exposure significantly diminished measurable cytokine polyfunctionality in response to BCG, Bordetella pertussis and SEB stimulation. These data show for the first time, when adjusting for confounders, that exposure to HIV in utero is associated with significant alterations to CD4+ and CD8+T-cell immune responses in infants to vaccines and nonspecific antigens.