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Immune active cells with 4-1BB signal enhancement inhibit hepatitis B virus replication in noncytolytic manner

机译:具有4-1BB信号增强的免疫活性细胞抑制非胞间溶解方式的乙型肝炎病毒复制

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摘要

Immune active cells (IACs) have been shown to be an alternative immunotherapy for CHB patients. However, there is a practical problem of different expansion rate and function of HBV inhibition as individual variability exists. Our previous studies have confirmed that the proliferation and cytolysis of IACs were significantly upregulated by engineered cells for costimulatory enhancement (ECCE) delivering a 4-1BB zeta activating signal. In this study, we aimed to investigate the contribution of ECCE to IACs from CHB patients. We found that ECCE could enhance larger-scale expansion of IACs and the levels of HBV-markers were reduced prominently with minimal cytolysis, in the indirect system which separated ECCE-IACs and HepG2.2.15 by a 0.4-mu m membrane. Furthermore, ECCE-IACs produced a lot of IFN-gamma and TNF-alpha. Blockading them, the inhibition was abrogated. These results provide direct evidence that ECCE-IACs efficiently control HBV replication in a noncytolytic manner, and this effect is mediated by IFN-gamma and TNF-alpha.
机译:已显示免疫活性细胞(IACS)是CHB患者的替代免疫疗法。然而,随着个体可变性存在,存在不同的膨胀率和HBV抑制功能的实际问题。我们之前的研究证实,IACS的增殖和细胞分解是通过工程细胞显着上调,用于递送4-1BB Zeta激活信号的共拖递增强(ECCE)。在这项研究中,我们旨在调查eCCE对CHB患者IACS的贡献。我们发现eCCE可以增强IACS的大规模扩张,并且在间接系统中,在间接体系中,在间接体系中,将HBV标记的水平降低,其间接体系将ECCE-IACS和HepG2.2.15分开0.4μm膜。此外,ECCE-IACS产生了许多IFN-GAMMA和TNF-α。阻断它们,抑制废除。这些结果提供了直接证据,即Ecce-IACS以非胞间溶解的方式有效地控制HBV复制,并且这种效果由IFN-Gamma和TNF-α介导。

著录项

  • 来源
    《Cellular immunology》 |2018年第2018期|共7页
  • 作者单位

    Southeast Univ Hosp Nanjing 2 Canc Res &

    Biotherapy Ctr Med Sch Zhong Fu Rd Nanjing 210003;

    Southeast Univ Med Sch Hosp Nanjing 2 Surg Dept Zhong Fu Rd Nanjing 210003 Jiangsu Peoples R;

    Danyang Peoples Hosp Infect Dept 2 Xinmin West Rd Danyang City 212300 Zhenjiang Peoples R China;

    Southeast Univ Hosp Nanjing 2 Canc Res &

    Biotherapy Ctr Med Sch Zhong Fu Rd Nanjing 210003;

    Southeast Univ Hosp Nanjing 2 Canc Res &

    Biotherapy Ctr Med Sch Zhong Fu Rd Nanjing 210003;

    Southeast Univ Med Sch Hosp Nanjing 2 Liver Dis Dept Zhong Fu Rd Nanjing 210003 Jiangsu;

    Southeast Univ Med Sch Hosp Nanjing 2 Liver Dis Dept Zhong Fu Rd Nanjing 210003 Jiangsu;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Adoptive immunocyte therapy; Immune active cells; Hepatitis B virus; 4-1BB/4-1BB zeta;

    机译:采用免疫细胞疗法;免疫活性细胞;乙型肝炎病毒;4-1bb / 4-1bb zeta;

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