NK细胞表型的调制和NK / T细胞相互作用的核苷（酸）类似物IDE

StephenW

Hepatology. 2015 Sep 11. doi: 10.1002/hep.28155. [Epub ahead of print]
NK cell phenotype modulation and NK/T cell interplay in nucleos(t)ide analogue treated HBeAg- patients with chronic hepatitis B.Boni C1, Lampertico P2, Talamona L1, Giuberti T1, Invernizzi F2, Barili V1, Fisicaro P1, Rossi M1, Cavallo MC1, Vecchi A1, Pedrazzi G3, Alfieri A1, Colombo M2, Missale G1, Ferrari C1.
Author information

• 1Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
• 2Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Italy.
• 3Department of Neuroscience - Biophysics and Medical Physics Unit, University of Parma, Parma, Italy.
  

AbstractNK and HBV-specific T cells are functionally impaired in chronic hepatitis B. Understanding to what extent NUC therapy can improve T and NK cell responses is important in the perspective of immunomonitoring strategies for a safe and earlier NUC withdrawal and of novel combination therapies based on the modulation of antiviral immunity. To gain further insights into T/NK cell interplay, we studied NK cell phenotype and function in HBeAg- chronic HBV patients either untreated (25) or NUC-treated (36 HBsAg+ and 10 HBsAg-/anti-HBs+). IFN-g, IL-2, and TNF-a production by HBV-specific T cells was also analysed in NUC treated patients. NK cells from chronic naive patients showed an "inflammatory" phenotype defined by increased expression of TRAIL, CD38 and Ki67 that significantly declined upon viremia suppression and ALT normalization induced by NUC therapy. Reversion to a quiescent NK cell phenotype was associated with restoration of the HBV-specific T cell function. T cell and NK cell responses showed an inverse correlation, with an opposite behavior in individual NUC treated patients. NK cell depletion as well as TRAIL and NKG2D pathway blockade induced a significant improvement of the HBV-specific T cell function.
CONCLUSIONS: NK cells can express regulatory activity on T cells in NUC treated patients with prevalent inhibition of CD4 T cells, likely needed to limit persistent T cell activation. NK cell phenotype is modulated by NUC therapy and its reversion to quiescence mirrors efficient HBV-specific T cell responses. Thus, changes of NK cell phenotype may predict acquisition of anti-viral control before anti-HBs seroconversion and represent the groundwork for future studies aimed at assessing whether NK phenotyping can be translated into the clinical practice to guide NUC suspension. This article is protected by copyright. All rights reserved.
© 2015 by the American Association for the Study of Liver Diseases.


KEYWORDS: HBV; HBsAg; NK cells; Nucleos(t)ide analogues; T cells

StephenW

肝病。 2015年九月11 DOI：10.1002 / hep.28155。 [打印EPUB提前]
NK细胞表型的调制和NK / T细胞相互作用的核苷（酸）类似物IDE治疗HBeAg-的慢性乙型肝炎患者B.
博尼C1，Lampertico P2，L1塔拉莫纳，Giuberti T1，Invernizzi F2，Barili V1，Fisicaro P1，罗西M1，卡瓦略MC1，韦基A1，Pedrazzi G3，阿尔菲力A1，科伦坡M2，Missale G1，法拉利C1。
作者信息

    1Laboratory病毒免疫病理学，传染病单位和肝病，Azienda与Ospedaliero-Universitaria di Parma的，帕尔马，意大利。
    2区学和免疫，基金会IRCCS钙'格兰达，Ospedale马焦雷位于Policlinico如Università德利阿布鲁Studi住宅米兰，意大利。
    3Department神经科学 - 生物物理与医学物理单位，帕尔马大学，帕尔马，意大利。

抽象的

NK和HBV特异性T细胞功能受损慢性乙型肝炎认识到什么程度的NUC治疗可以改善T细胞和NK细胞应答是在immunomonitoring策略基于所述立体对的新的组合疗法安全和更早NUC撤回和重要抗病毒免疫的调制。为了获得进一步的见解入T / NK细胞相互作用，我们研究了NK细胞的表型和功能的个HBeAg-的慢性HBV患者未处理（25）或NUC处理（36的HBsAg +和10 HBsAg- /抗HBs +）。 IFN-γ的IL-2，以及由HBV特异性T细胞TNF-α产生还分析在NUC治疗的患者。慢性初治患者NK细胞表现出由TRAIL，CD38和Ki67的表达增加在病毒血症抑制和诱导NUC治疗ALT复常说显著下跌定义的“炎症”的表型。回复到静止NK细胞表型与恢复HBV特异性T细胞功能的相关联。 T细胞和NK细胞的反应呈负相关，与在个体NUC一个相反的行为治疗的患者。 NK细胞耗尽以及TRAIL与NKG2D通路封锁诱导了显著改善HBV特异性T细胞功能的。
结论：

NK细胞可表达在NUC治疗患者普遍抑制CD4 + T细胞，可能需要限制持久性T细胞的活化T细胞上的调节活性。 NK细胞的表型是由NUC疗法及其逆转调制以静止镜高效HBV特异性T细胞应答。因此，NK细胞表型的变化可能预测采集的抗病毒控制抗HBs血清转换前的，并代表了基础未来的研究，目的是评估的NK表型是否可以被翻译成的临床实践中，以指导NUC悬浮液​​。这篇文章是受版权保护的。版权所有。

©2015年肝病研究的美国协会。
关键词：

乙肝病毒;乙肝表面抗原; NK细胞;核苷（酸）类似物; T细胞