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年龄相关的健康儿童对卡介苗免疫反应的减弱支持在结核病流行国家需要加强卡介苗剂量。

Age-related waning of immune responses to BCG in healthy children supports the need for a booster dose of BCG in TB endemic countries.

机构信息

Academic Department of Paediatrics, St Marys Campus, Imperial College London, 2nd Floor Wright-Fleming Building, Norfolk Place, London, W2 1PG, UK.

Division of Medical Microbiology, Department of Pathology And Institute of Infectious Disease and Molecular Medicine UCT Faculty of Health Sciences, Observatory, 7925, South Africa.

出版信息

Sci Rep. 2018 Oct 17;8(1):15309. doi: 10.1038/s41598-018-33499-4.


DOI:10.1038/s41598-018-33499-4
PMID:30333506
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6193026/
Abstract

In the absence of a more effective vaccine against TB and in the interest of developing one, it is essential to understand immune responses associated with BCG protection. We comprehensively characterized T cell populations in BCG-vaccinated children over time. Blood from 78 healthy, BCG-vaccinated children representing four age groups (<1 yr, ≥1 yr <2 yr, ≥2 yr <5 yr, ≥5 yr), was stimulated in vitro for 24 hours and 6 days with live BCG to induce effector and central memory responses. Antigen-specific CD4, CD8, γδ and regulatory T cell populations were phenotyped and intracellular and secreted cytokines measured by flow cytometry and multiplex ELISA respectively. Our results demonstrated that populations of naïve T cells predominated in infants, compared to older children. However, BCG-specific effector CD4 T cell responses were equivalent and antigen-specific CD4 T cell proliferative capacity was increased in infants compared to older children. Increases in innate immune responses including γδ T cell responses and secreted pro-inflammatory cytokines were noted with increasing age. In conclusion, we identified that the capacity to expand and differentiate effector T cells in response to BCG stimulation wanes with increasing age, which may indicate waning central memory immunity. Booster vaccination could be considered to maintain the antigen-specific central memory pool and possibly enhance the duration of protection.

摘要

在缺乏更有效的结核病疫苗的情况下,为了开发这种疫苗,了解与卡介苗保护相关的免疫反应至关重要。我们全面描述了随时间推移卡介苗接种儿童的 T 细胞群体。从 78 名健康、接种过卡介苗的儿童(<1 岁、≥1 岁<2 岁、≥2 岁<5 岁、≥5 岁)中采集血液,用活卡介苗在体外刺激 24 小时和 6 天,以诱导效应和中央记忆反应。通过流式细胞术和多重 ELISA 分别对抗原特异性 CD4、CD8、γδ 和调节性 T 细胞群体进行表型分析,并测量细胞内和分泌的细胞因子。我们的研究结果表明,与年龄较大的儿童相比,婴儿中幼稚 T 细胞群体占优势。然而,卡介苗特异性效应 CD4 T 细胞反应相当,并且与年龄较大的儿童相比,婴儿的抗原特异性 CD4 T 细胞增殖能力增加。随着年龄的增长,先天免疫反应(包括 γδ T 细胞反应和分泌的促炎细胞因子)增加。总之,我们发现,随着年龄的增长,针对卡介苗刺激而扩张和分化效应 T 细胞的能力会减弱,这可能表明中央记忆免疫减弱。可以考虑加强免疫接种以维持抗原特异性中央记忆池,并可能延长保护期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/8ec0f2637bce/41598_2018_33499_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/cd7020543926/41598_2018_33499_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/1a9d2f446e05/41598_2018_33499_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/442175672388/41598_2018_33499_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/7cb362118279/41598_2018_33499_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/8ec0f2637bce/41598_2018_33499_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/cd7020543926/41598_2018_33499_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/1a9d2f446e05/41598_2018_33499_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/442175672388/41598_2018_33499_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/7cb362118279/41598_2018_33499_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/6193026/8ec0f2637bce/41598_2018_33499_Fig5_HTML.jpg

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