干细胞衍生的病毒银特异性T淋巴细胞抑制小鼠中的HBV复制。

StephenW

J Vis Exp. 2019 Sep 25;(151). doi: 10.3791/60043.
Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice.
Xiong X1, Lei F2, Haque M1, Song J3.
Author information

1
    Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center.
2
    Department of Ophthalmology, Harvard Medical School.
3
    Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center; [email protected].

Abstract

Hepatitis B virus (HBV) infection is a global health issue. With over 350 million people affected worldwide, HBV infection remains the leading cause of liver cancer. This is a major concern, especially in developing countries. Failure of the immune system to mount an effective response against HBV leads to chronic infection. Although HBV vaccine is present and novel antiviral medicines are being created, eradication of virus-reservoir cells remains a major health topic. Described here is a method for the generation of viral antigen (Ag) -specific CD8+ cytotoxic T lymphocytes (CTLs) derived from induced pluripotent stem cells (iPSCs) (i.e., iPSC-CTLs), which have the ability to suppress HBV replication. HBV replication is efficiently induced in mice through hydrodynamic injection of an HBV expression plasmid, pAAV/HBV1.2, into the liver. Then, HBV surface Ag-specific mouse iPSC-CTLs are adoptively transferred, which greatly suppresses HBV replication in the liver and blood as well as prevents HBV surface Ag expression in hepatocytes. This method demonstrates HBV replication in mice after hydrodynamic injection and that stem cell-derived viral Ag-specific CTLs can suppress HBV replication. This protocol provides a useful method for HBV immunotherapy.

PMID:
    31609353
DOI:
    10.3791/60043

StephenW

J Vis Exp。 2019年9月25日;（151）。 doi：10.3791 / 60043。
干细胞衍生的病毒银特异性T淋巴细胞抑制小鼠中的HBV复制。
熊X1，雷F2，哈克M1，宋J3。
作者信息

1个
    德州农工大学健康科学中心微生物发病机制和免疫学系。
2
    哈佛医学院眼科。
3
    德州农工大学健康科学中心微生物发病机制和免疫学系； [email protected]。

抽象

乙型肝炎病毒（HBV）感染是全球性的健康问题。全世界有超过3.5亿人受到感染，HBV感染仍然是肝癌的主要原因。这是一个主要问题，特别是在发展中国家。免疫系统未能有效抵抗HBV导致慢性感染。尽管目前存在HBV疫苗并正在开发新的抗病毒药物，但是消灭病毒储存细胞仍然是主要的健康主题。这里描述的是一种产生自诱导多能干细胞（iPSC）（即iPSC-CTL）的病毒抗原（Ag）特异性CD8 +细胞毒性T淋巴细胞（CTL）的方法，该方法具有抑制HBV复制的能力。通过将HBV表达质粒pAAV / HBV1.2流体动力学注射入肝脏，可在小鼠中有效诱导HBV复制。然后，HBV表面Ag特异的小鼠iPSC-CTL被过继转移，这极大地抑制了HBV在肝脏和血液中的复制，并阻止了HBV表面Ag在肝细胞中的表达。这种方法证明了在流体动力注射后小鼠中的HBV复制，并且干细胞来源的病毒Ag特异性CTL可以抑制HBV复制。该协议为HBV免疫疗法提供了一种有用的方法。

PMID：
    31609353
DOI：
    10.3791 / 60043