Science子刊封面:HIV感染引发免疫细胞“失效”的细节
2018/04/09
4月6日,《Science Immunology》期刊以封面形式发表了一篇文章,揭示一种关键的免疫细胞在艾滋病患者体内失效的细节。虽然这一细胞数量z在艾滋病患者体内远多于健康人群,但是因为HIV的感染,该细胞出现功能障碍。


图片来源:Science Immunology(DOI: 10.1126/sciimmunol.aan8884)

这一最新研究关注的“主角”是滤泡辅助性T细胞(Tfh)——一类新的CD4+T细胞亚群,负责向B细胞传递信号,促使后者分化成浆细胞和记忆B细胞,进而产生抵抗HIV等病毒的入侵。

遗憾的是,来自于德克萨斯大学奥斯汀分校Cockrell工程学院、宾夕法尼亚大学的的科学家们发现,艾滋病患者体内的Tfh细胞“失效”了。

根据世界卫生组织的最新数据,全世界大约有4000万人感染了艾滋病毒。近年来,得益于医学的进步和公共意识的提高,登记在册的病例数量一直在稳步下降。然而,我们对于HIV病毒的致病机制依然存在很大的空白,因此每一次的新发现都很重要。


HIV infection impacts the normal function of follicular T cell. Credit: Carla Shaffer / AAAS

最新研究表明,艾滋病患者淋巴结中的Tfh细胞数量远远多于正常人。理论上,基于Tfh细胞产生保护性抗体的核心作用,数量的增加会增强其对病毒的抵抗。然而,借助复杂的测序技术以及大规模的细胞测量方法,生物医学工程系助理教授Ning Jiang、医学院助理教授Laura F. Su和团队直接检测了Tfh细胞应对HIV的反应,发现事实并非如此——患者体内的Tfh细胞并没有发挥抵抗病毒感染的正常功能。

“正常情况下,Tfh细胞与其他免疫细胞交流,并向B细胞传递指令,例如产生病毒中和抗体(不仅对抗病毒,还有助于防御未来的感染)。” Ning Jiang解释道。

但是,在HIV患者淋巴结中,Tfh细胞的多功能性较低。而且,这种功能缺失与B细胞类别转换受损有关。

研究人员认为,相比于抵抗类似于普通感冒一样的急性感染,Tfh细胞面对HIV等慢性感染时会表现出不同的行为。下一步,他们将试图进一步解析Tfh细胞失效的原因,从而更好地了解HIV。

责编:悠然

参考资料:

HIV cell dysfunction discovery sheds light on how virus works

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  • The receptor repertoire and functional profile of follicular T cells in HIV-infected lymph nodes

    Follicular helper CD4+ T cells (TFH) play an integral role in promoting B cell differentiation and affinity maturation. Whereas TFH cell frequencies are increased in lymph nodes (LNs) from individuals infected with HIV, humoral immunity remains impaired during chronic HIV infection. Whether HIV inhibits TFH responses in LNs remains unclear. Advances in this area have been limited by the difficulty of accessing human lymphoid tissues. Here, we combined high-dimensional mass cytometry with T cell receptor repertoire sequencing to interrogate the composition of TFH cells in primary human LNs. We found evidence for intact antigen-driven clonal expansion of TFH cells and selective utilization of specific complementarity-determining region 3 (CDR3) motifs during chronic HIV infection, but the resulting TFH cells acquired an activation-related TFH cell signature characterized by interleukin-21 (IL-21) dominance. These IL-21+ TFH cells contained an oligoclonal HIV-reactive population that preferentially accumulated in patients with severe HIV infection and was associated with aberrant B cell distribution in the same LN. These data indicate that TFH cells remain capable of responding to HIV antigens during chronic HIV infection but become functionally skewed and oligoclonally restricted under persistent antigen stimulation.

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