Th1/Th17 cell induction and corresponding reduction in ATP consumption following vaccination with the novel Mycobacterium tuberculosis vaccine MVA85A.
Th1/Th17 cell induction and corresponding reduction in ATP consumption following vaccination with the novel Mycobacterium tuberculosis vaccine MVA85A.
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DOI：
10.1371/journal.pone.0023463
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
McShane H
中科院分区：
文献类型：
--
作者：
Griffiths KL;Pathan AA;Minassian AM;Sander CR;Beveridge NE;Hill AV;Fletcher HA;McShane H
卡介苗（BCG）接种传统上用于预防结核分枝杆菌（M.tb）引起的疾病。卡介苗的疗效，特别是对肺结核（TB）的疗效是可变的。最好的保护是在温带气候中，在结核和非结核分枝杆菌物种高度流行的许多热带地区几乎没有保护。尽管已知干扰素（IFN）-γ在预防TB疾病中是重要的，但在鼠和牛TB疫苗研究以及在人类中，关于白细胞介素（IL）-17作为关键细胞因子的可能作用的数据正在出现。表达抗原85 A的改良安卡拉痘苗病毒（MVA 85 A）是一种新型结核病疫苗，旨在增强卡介苗诱导的应答。已经显示抗原特异性IFN-γ产生在MVA 85 A疫苗接种后一周达到峰值，并且先前已经描述了IL-17产生细胞和表达外核苷酶CD 39的调节性T细胞之间的反比关系，所述外核苷酶CD 39代谢促炎性细胞外ATP。本文探讨了这种关系，发现MVA 85 A疫苗接种受试者的外周血单核细胞消耗的细胞外ATP在疫苗接种后两周下降，对应于表达外核苷酶CD 39的调节性T细胞亚群的百分比下降。同样在该时间点，我们报告了由CD 4 + T细胞共同产生IL-17和IFN-γ的峰值。这些结果表明细胞外ATP和效应子应答之间的关系，并揭示了疫苗设计期间可能靶向的可能途径。
Vaccination with Bacille Calmette-Guérin (BCG) has traditionally been used for protection against disease caused by the bacterium Mycobacterium tuberculosis (M.tb). The efficacy of BCG, especially against pulmonary tuberculosis (TB) is variable. The best protection is conferred in temperate climates and there is close to zero protection in many tropical areas with a high prevalence of both tuberculous and non-tuberculous mycobacterial species. Although interferon (IFN)-γ is known to be important in protection against TB disease, data is emerging on a possible role for interleukin (IL)-17 as a key cytokine in both murine and bovine TB vaccine studies, as well as in humans. Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) is a novel TB vaccine designed to enhance responses induced by BCG. Antigen-specific IFN-γ production has already been shown to peak one week post-MVA85A vaccination, and an inverse relationship between IL-17-producing cells and regulatory T cells expressing the ectonucleosidease CD39, which metabolises pro-inflammatory extracellular ATP has previously been described. This paper explores this relationship and finds that consumption of extracellular ATP by peripheral blood mononuclear cells from MVA85A-vaccinated subjects drops two weeks post-vaccination, corresponding to a drop in the percentage of a regulatory T cell subset expressing the ectonucleosidase CD39. Also at this time point, we report a peak in co-production of IL-17 and IFN-γ by CD4+ T cells. These results suggest a relationship between extracellular ATP and effector responses and unveil a possible pathway that could be targeted during vaccine design.
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影响因子：
30.5
作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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通讯作者：
Surprenant, Annmarie