Bacillus Calmette-Guérin Vaccination of Human Newborns Induces T Cells with Complex Cytokine and Phenotypic Profiles1
Bacillus Calmette-Guérin Vaccination of Human Newborns Induces T Cells with Complex Cytokine and Phenotypic Profiles1
复制标题
对人类新生儿进行卡介苗疫苗接种可诱导具有复杂细胞因子和表型特征的 T 细胞1
作者：
Andreia P Soares;T. Scriba;S. Joseph;Ryhor Harbacheuski;R. Murray;S. Gelderbloem;A. Hawkridge;G. Hussey;H. Maecker;G. Kaplan;W. Hanekom
接种卡介苗（BCG）是唯一可用的结核病疫苗，其免疫反应尚未得到充分表征。我们使用多参数流式细胞术检测出生时常规接种卡介苗的10周龄婴儿血液中特异性T细胞细胞因子的产生和表型特征。用BCG离体刺激全血12 h，在7种不同的细胞因子组合中诱导CD 4 + T细胞中主要表达IFN-γ、IL-2和TNF-α。IL-4和IL-10的表达在CD 4 + T细胞中以低频率检测，并且仅在不共表达1型细胞因子的细胞中检测。特异性CD 8 + T细胞的频率低于CD 4 + T细胞，主要产生IFN-γ和/或IL-2，而产生较少的TNF-α、IL-4和IL-10。重要的是，许多分枝杆菌特异性CD 4+和CD 8 + T细胞不产生IFN-γ。BCG特异性1型T细胞的主要表型是效应细胞，即，CD 45 RA − CCR 7 − CD 27+，这可能反映了牛分枝杆菌BCG在婴儿中的持续存在，直到10周龄。在CD 4 + T细胞的5种表型中，中枢记忆细胞更可能是IL-2+，效应细胞更可能是IFN-γ+。我们的结论是，新生儿接种卡介苗诱导T细胞的细胞因子表达和表型的复杂模式。单独测量IFN-γ的产生低估了宿主细胞因子对BCG疫苗接种的反应的程度和复杂性，并且在BCG和新型结核病疫苗接种的研究中可能不是最佳的读数。
The immune response to vaccination with bacillus Calmette-Guérin (BCG), the only tuberculosis vaccine available, has not been fully characterized. We used multiparameter flow cytometry to examine specific T cell cytokine production and phenotypic profiles in blood from 10-wk-old infants routinely vaccinated with BCG at birth. Ex vivo stimulation of whole blood with BCG for 12 h induced expression of predominantly IFN-γ, IL-2, and TNF-α in CD4+ T cells in seven distinct cytokine combinations. IL-4 and IL-10 expression was detected in CD4+ T cells at low frequencies and only in cells that did not coexpress type 1 cytokines. Specific CD8+ T cells were less frequent than CD4+ T cells and produced mainly IFN-γ and/or IL-2 and less TNF-α, IL-4, and IL-10. Importantly, many mycobacteria-specific CD4+ and CD8+ T cells did not produce IFN-γ. The predominant phenotype of BCG-specific type 1 T cells was that of effector cells, i.e., CD45RA−CCR7−CD27+, which may reflect persistence of Mycobacterium bovis BCG in infants until 10 wk of age. Among five phenotypic patterns of CD4+ T cells, central memory cells were more likely to be IL-2+ and effector cells were more likely to be IFN-γ+. We concluded that neonatal vaccination with BCG induces T cells with a complex pattern of cytokine expression and phenotypes. Measuring IFN-γ production alone underestimates the magnitude and complexity of the host cytokine response to BCG vaccination and may not be an optimal readout in studies of BCG and novel tuberculosis vaccination.
影响因子：
20.3
作者：
Betts, Michael R.;Nason, Martha C.;Koup, Richard A.
通讯作者：
Koup, Richard A.
影响因子：
15.9
作者：
Boussiotis, VA;Tsai, EY;Goldfeld, AE
通讯作者：
Goldfeld, AE
影响因子：
3.2
作者：
Flynn, JL
通讯作者：
Flynn, JL