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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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Published in: | Archives of virology 2018-04, Vol.163 (4), p.855-865 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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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. |
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ISSN: | 0304-8608 1432-8798 |
DOI: | 10.1007/s00705-017-3675-8 |