Ye Li, Wang Xu, Wang Shihong, Wang Yanjian, Song Li, Hou Wei, Zhou Lin, Li He, Ho Wenzhe
Department of Pediatrics, Division of Allergy and Immunology, Joseph Stokes, Jr Research Institute at The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Hepatology. 2009 Mar;49(3):753-62. doi: 10.1002/hep.22715.
CD56(+) T cells are abundant in liver and play an important role in defense against viral infections. However, the role of CD56(+) T cells in control of hepatitis C virus (HCV) infection remains to be determined. We investigated the noncytolytic anti-HCV activity of primary CD56(+) T cells in human hepatocytes. When HCV Japanese fulminant hepatitis-1 (JFH-1)-infected hepatocytes were co-cultured with CD56(+) T cells or incubated in media conditioned with CD56(+) T cell culture supernatants (SN), HCV infectivity and replication were significantly inhibited. The antibodies to interferon (IFN)-gamma or IFN-gamma receptor could largely block CD56(+) T cell-mediated anti-HCV activity. Investigation of mechanism(s) responsible for CD56(+) T cell-mediated noncytolytic anti-HCV activity showed that CD56(+) T SN activated the multiple elements of janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and enhanced the expression of IFN regulatory factors (IRFs) 1, 3, 7, 8, and 9, resulting in the induction of endogenous IFN-alpha/beta expression in hepatocytes. Moreover, CD56(+) T SN treatment inhibited the expression of HCV-supportive micro RNA (miRNA)-122 and enhanced the levels of anti-HCV miRNA-196a in human hepatocytes.
These findings provide direct in vitro evidence at cellular and molecular levels that CD56(+) T cells may have an essential role in innate immune cell-mediated defense against HCV infection. (HEPATOLOGY 2009.).
CD56(+) T细胞在肝脏中大量存在，在抵御病毒感染中发挥重要作用。然而，CD56(+) T细胞在丙型肝炎病毒（HCV）感染控制中的作用仍有待确定。我们研究了原代CD56(+) T细胞在人肝细胞中的非细胞溶解抗HCV活性。当HCV日本暴发性肝炎-1（JFH-1）感染的肝细胞与CD56(+) T细胞共培养或在含有CD56(+) T细胞培养上清液（SN）的培养基中孵育时，HCV感染性和复制受到显著抑制。抗干扰素（IFN）-γ或IFN-γ受体的抗体可在很大程度上阻断CD56(+) T细胞介导的抗HCV活性。对负责CD56(+) T细胞介导的非细胞溶解抗HCV活性的机制研究表明，CD56(+) T SN激活了Janus激酶/信号转导和转录激活因子（JAK/STAT）途径的多个元件，并增强了干扰素调节因子（IRF）1、3、7、8和9的表达，导致肝细胞中内源性IFN-α/β表达的诱导。此外，CD56(+) T SN处理抑制了支持HCV的微小RNA（miRNA）-122的表达，并提高了人肝细胞中抗HCV miRNA-196a的水平。
这些发现提供了细胞和分子水平的直接体外证据，表明CD56(+) T细胞可能在先天免疫细胞介导的抗HCV感染防御中起重要作用。（《肝脏病学》杂志2009年）
