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Contradictory intrahepatic immune responses activated in high-load hepatitis C virus livers compared with low-load livers

We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain ( HLA-DQA1 ), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examin...

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Bibliographic Details
Published in:Archives of virology 2018-04, Vol.163 (4), p.855-865
Main Authors: Ishibashi, Mariko, Yamaguchi, Hiromi, Hirotani, Yukari, Sakurada, Akihisa, Endo, Toshihide, Sugitani, Masahiko, Takayama, Tadatoshi, Makishima, Makoto, Esumi, Mariko
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Language:English
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Summary:We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain ( HLA-DQA1 ), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area. Parenchymal hepatocytes were negative for HLA-DQA1. HLA-DQA1-positive cells in the liver sinusoid were positive for CD68 (macrophages or Kupffer cells); those in the lymphocytic infiltrates were positive for CD20 (B cells) or CD3 (T cells). mRNA levels of antigen-presenting cell (APC) markers such as CD68 and CD11c were significantly upregulated in the HCV-high group and were correlated with HLA-DQA mRNA levels. CD8B mRNA (CD8 + T cells) was upregulated in both HCV-positive livers compared with HCV-negative livers, whereas CD154 mRNA (CD4 + T helper cell) was upregulated in the HCV-high group compared with the HCV-low group. The immune regulatory molecules FOXP3 mRNA (regulatory T cell, T reg) and programmed cell death ligand-1 ( PD-L1 ) mRNA were significantly increased in the HCV-high group. HCV-high livers had two molecular immune responses: increased APC numbers and adaptive immunity and the induction of immune tolerance. The local hepatic imbalance of contradictory immune responses might be responsible for high HCV loads.
ISSN:0304-8608
1432-8798
DOI:10.1007/s00705-017-3675-8