除感染阶段外，HBV特异性T细胞的表型和功能由靶表位决定。

StephenW

Gut. 2018 Dec 22. pii: gutjnl-2018-316644. doi: 10.1136/gutjnl-2018-316644. [Epub ahead of print]
Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection.
Hoogeveen RC1,2, Robidoux MP1, Schwarz T3, Heydmann L4, Cheney JA1, Kvistad D1, Aneja J1, Melgaço JG5, Fernandes CA6, Chung RT1, Boonstra A2, Kim AY7, Baumert TF4, Timm J3, Lewis-Ximenez LL5, Tonnerre P#1, Lauer GM#1.
Author information

1
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
2
    Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
3
    Institute of Virology, Heinrich Heine University, University Hospital, Düsseldorf, Germany.
4
    Institut de Recherche sur les Maladies Virales et Hépatiques, Inserm U1110, Strasbourg, France.
5
    Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
6
    Laboratório Central de Saúde Pública Noel Nutels, Rio de Janeiro, Brazil.
7
    Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
#
    Contributed equally

Abstract
OBJECTIVE:

Chronic HBV infection affects more than 250 million people worldwide and remains a global healthcare problem in part because we lack curative treatment. Sustained viral control requires HBV-specific T cells, but these become functionally impaired in chronic infection. Clinical evidence indicates that functional cure of HBV infection by the host immune response is feasible. Developing T cell-based therapies able to achieve functional cure will require identification of the requirements for a successful T cell response against HBV and the relative contribution of individual T cell specificities to HBV control.
DESIGN:

The phenotype and function of HBV-specific T cells were studied directly ex vivo using fluorochrome-labelled multimers. We studied multiple HBV-specific T cell specificities targeting different HBV proteins in individuals with either an acute self-limiting or chronic HBV infection.
RESULTS:

We detected strong T cell responses targeting multiple HBV viral proteins in acute self-limiting and low-frequency core and polymerase-specific T cells in chronic infection. Expression of the T cell inhibitory receptor PD-1, as well as T cell differentiation, T cell function and T cell regulation differed by stages and outcomes of infection. In addition, these features differed significantly between T cells targeting different HBV specificities.
CONCLUSION:

HBV-specific T cells with different target specificities are characterised by distinct phenotypical and functional profiles. These results have direct implications for the design of immunological studies in HBV infection, and are potentially relevant for informing immunotherapeutic approaches to induce functional cure.

© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS:

acute hepatitis; cellular immunity; chronic hepatitis; hepatitis B

PMID:
    30580250
DOI:
    10.1136/gutjnl-2018-316644

StephenW

肠道。 2018年12月22日.pii：gutjnl-2018-316644。 doi：10.1136 / gutjnl-2018-316644。 [提前打印]
除感染阶段外，HBV特异性T细胞的表型和功能由靶表位决定。
Hoogeveen RC1,2，Robidoux MP1，Schwarz T3，Heydmann L4，Cheney JA1，Kvistad D1，Aneja J1，MelgaçoJG5，Fernandes CA6，Chung RT1，Boonstra A2，Kim AY7，Baumert TF4，Timm J3，Lewis-Ximenez LL5，Tonnerre P＃1，Lauer GM＃1。
作者信息

1
    马萨诸塞州综合医院消化内科和美国马萨诸塞州波士顿哈佛医学院。
2
    荷兰鹿特丹Erasmus MC消化内科和肝病学系。
3
    德国杜塞尔多夫大学医院海因里希海涅大学病毒学研究所。
4
    Institut de Recherche sur les Maladies ViralesetHépatiques，Inserm U1110，Strasbourg，France。
五
    FundaçãoOswaldoCruz，Instituto Oswaldo Cruz，巴西里约热内卢。
6
    巴西里约热内卢巴西中央电力公司实验室。
7
    马萨诸塞州综合医院传染病科和美国马萨诸塞州波士顿哈佛医学院。
＃
    贡献一致

抽象
目的：

慢性HBV感染影响全球超过2.5亿人，并且仍然是全球医疗保健问题，部分原因是我们缺乏治疗性治疗。持续的病毒控制需要HBV特异性T细胞，但这些在慢性感染中功能受损。临床证据表明，通过宿主免疫应答功能性治愈HBV感染是可行的。开发能够实现功能性治愈的基于T细胞的疗法将需要鉴定针对HBV的成功T细胞应答的要求以及个体T细胞特异性对HBV控制的相对贡献。
设计：

使用荧光染料标记的多聚体直接离体研究HBV特异性T细胞的表型和功能。我们研究了针对具有急性自限性或慢性HBV感染的个体中针对不同HBV蛋白的多种HBV特异性T细胞特异性。
结果：

我们在慢性感染的急性自限性和低频核心和聚合酶特异性T细胞中检测到针对多种HBV病毒蛋白的强T细胞应答。 T细胞抑制性受体PD-1的表达，以及T细胞分化，T细胞功能和T细胞调节因感染的阶段和结果而不同。此外，这些特征在靶向不同HBV特异性的T细胞之间存在显着差异。
结论：

具有不同靶特异性的HBV特异性T细胞的特征在于不同的表型和功能特征。这些结果对于HBV感染的免疫学研究的设计具有直接意义，并且可能与通知免疫治疗方法诱导功能性治愈有关。

©作者（或其雇主）2018。无商业再利用。请参阅权限。由BMJ发布。
关键词：

急性肝炎;细胞免疫;慢性肝炎;乙型肝炎

结论：
    30580250
DOI：
    10.1136 / gutjnl-2018-316644