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Human Hepatocytes are Capable of Expressing B7 Family Inhibitory Ligands
Author(s) -
Kassel Rachel,
Taylor Nicholas A,
Hahn Young S
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.858.13
Subject(s) - cd8 , hepatitis c virus , mhc class i , biology , hepatocyte , mhc class ii , t cell , major histocompatibility complex , cell culture , immunology , cytotoxic t cell , virology , virus , antigen , microbiology and biotechnology , immune system , genetics , in vitro
Hepatitis C virus (HCV) establishes persistent infection in 70% of acutely infected individuals. Hepatocytes, the primary site of infection, potentially contribute to the impaired T cell responses that characterize progression to chronic infection. We hypothesize that HCV‐infected hepatocytes express PD and related ligands that signal to CD8 + T cells; CD8 + T cells have been reported to up‐regulate PD‐1 in chronically infected patients. To this end, expression of B7 family members and MHC Class I were examined on Huh 7.5 cells and primary hepatocytes following culture in conditions mimicking the HCV‐infected liver environment. Wild type Huh 7.5 cells (a hepatoma cell line) as well as those containing full‐length (FL) or the non‐structural region of HCV were cultured in the presence or absence of IFN‐γ for 24‐48 hours. Huh 7.5 cells responded to IFN‐γ; they expressed PD‐L1 and MHC Class I following stimulation. Huh 7.5 cells expressed B7‐H3 independent of IFN‐γ stimulation and did not inducibly express PD‐L2. There was no significant difference in expression of B7‐H1, B7‐H3, or MHC Class I between wild‐type Huh 7.5 and those containing FL or sub‐genomic HCV constructs cultured +/– IFN‐γ. Importantly, cultured, non‐transformed primary hepatocytes expressed MHC Class I, B7‐H1, B7‐DC, and B7‐H3. This suggests that hepatocytes are capable of expressing negative stimulatory molecules under normal conditions and modulating expression under inflammatory conditions, resulting in impaired T cell responses. HCV infection may utilize this tolerogenic predisposition of the liver to establish chronic infection.