Sci Immun:新发现为改进HIV和丙肝疫苗提供新思路

2018-01-23 佚名 生物探索

近日,加州的研究人员发现了CD4细胞毒性T细胞是如何发展的,这或将打开改进艾滋病病毒和丙肝病毒疫苗设计的大门。相关研究结果在线发表在2018年1月19日的《Science Immunology》上。

新发现

多年来,世界各地的科学家们一直试图研制出有效的HIV和丙型肝炎疫苗,但收效都不尽如人意。目前,控制这些慢性病毒的唯一方法就是使用药物。

在这项最新研究中,美国拉霍亚过敏和免疫学研究所(LJI)的研究人员使用单细胞转录组分析,来鉴定迄今为止还不为人知的致命T细胞亚群的前体,这些细胞主要存在患有慢性病感染的人体内。他们详细分析了9000多个个体细胞中的转录基因组,也揭示了前所未有的异质性水平。

该研究领导者、LJI特聘教授K. William J. Bowes Jr博士说:“不断发展的基因组工具和单细胞分析技术正在彻底改变我们对人类免疫系统在健康和疾病中的理解。但这只是基因组旅程的开始,通过将这些工具应用于相关疾病和细胞类型,我们正在改变我们对人类免疫细胞生物学的理解。

据了解,基于细胞表面标记,即为CD4和CD8,T细胞通常分为两大类:CD4-阳性辅助T细胞(帮助激活其它免疫细胞)和CD8阳性细胞毒性T细胞(杀死癌细胞或感染的细胞与病毒)。

然而,在某些情况下,一部分辅助T细胞变成细胞毒性T细胞(CD4-CTL)。 CD4 CTL最初是在慢性病毒感染例如人巨细胞病毒(CMV)、HIV、登革热病毒和丙型肝炎病毒的人类中。

新工具

博士后研究员和第一作者Veena Patil博士表示,“我们观察到的细胞毒性CD4 T细胞与CD4辅助T细胞比例的增加,这表明它们是对病毒感染的保护性免疫应答的重要组成部分,它们的诱导应该是成功预防某些病毒性疾病的重要标志。但是我们对它们的分子结构和驱动它们的分化和维护机制知之甚少。”

为了解更多的信息,Patil使用单细胞RNA测序分析了从捐赠者外周血分离的数千个CD4-CTL,通过揭示个体细胞产生的转录产物的差异来定义不同的细胞类型和亚型。这些分析揭示了个体细胞和个体之间的显着异质性。她说:“这可能是由于我们研究对象的感染和病毒暴露时间的多样性以及基因多样性的影响。“

Vijayanand和他的研究小组发现了这组T细胞之前未知的前体,解释了CD4杀手T细胞是如何形成的,并可以帮助对HIV、hep C和巨细胞病毒等病毒的疫苗设计进行调整。

新思路

研制艾滋病毒和丙型肝炎疫苗一直是一个挑战,因为这两种病毒都是快速变异以逃避免疫系统的病毒。艾滋病疫苗项目和斯克里普斯研究所的科学家们正在关注病毒的变化和抗体特征,这可能成为艾滋病毒疫苗设计的蓝图。

与此同时,马里兰大学(University of Maryland)从美国国立卫生研究院(NIH)筹集了600万美元,用“基于结构的设计”来开发丙肝疫苗。这个想法是在原子水平上制造疫苗免疫原,以便“稳定”抗原并避免分散快速发展病毒的元素。

原始出处:

Veena S. Patil, Ariel Madrigal, Benjamin J. Schmiedel,et al. Precursors of human CD4+ cytotoxic T lymphocytes identified by single-cell transcriptome analysis. Science Immunology  19 Jan 2018: Vol. 3, Issue 19, eaan8664. DOI: 10.1126/sciimmunol.aan8664.

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    2018-12-23 晓辰
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    2018-01-23 天地飞扬

    了解一下.谢谢分享!

    0

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    2018-01-23 131****1460

    学习了受益匪浅

    0

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    2018-01-23 惠映实验室

    学习了.谢谢分享.

    0

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当下,通过高活性抗逆转录病毒疗法(HAART)使得艾滋病患者的生存率大幅提高。2017年发表在《J Am Coll Cardiol》上的一项研究,对引入HAART在HIV感染的儿童中的长期心血管影响进行了评估。

Thorax:HIV感染与气流限制分析!

由此可见,HIV是FEV1和FVC同时降低的危险因素。这种过度的风险不是由吸烟或社会经济状况来解释的,可能是由先前的免疫缺陷所介导的。