The hepatitis C virus (HCV) induces a long-term increase in interleukin-10 production by human CD4+ T cells (H9).
Patients with chronic hepatitis C present an imbalance of Th1/Th2 cytokine production. Therefore, we investigated whether the exposure of the CD4+ T cell line H9 to HCV could induce activation of cells through synthesis of IL-10. Three infection protocols were performed to enhance HCV propagation. Viral particles were prepared by ultracentrifugation of serum from patients. From 3 to 81 days post-infection (p.i.), HCV-RNA was monitored both in supernatants and cells by nested RT-PCR, IL-10 protein in medium by ELISA, and IL-10 mRNA in cells by semi-quantitative RT-PCR. The expression of tetraspanins was analyzed by flow cytometry. The PKC signal pathway was studied using specific inhibitors. The H9 cells express CD81. HCV-RNA (+) was detected in cells until 21 days p.i, and in culture media over 39 days p.i. Up to day 81 p.i., HCV exposure induced a specific, 2-fold increase of IL-10 production by H9 cells. IL-10 production was inhibited by a PKC inhibitor (Calphostin C). This study shows that even if the infection of H9 T cells did not result in any viral progeny, HCV induced the activation of IL-10 secretion, which supports the role of IL-10 in HCV pathogenesis.
INSERM E. 99-41, Centre Hépato-Biliaire, Hôpital Paul-Brousse, 12, avenue Paul-Vaillant Couturier, 94800 Villejuif, France.
O
O
Delpuech
D B
DB
Buffello-Le Guillou
E
E
Rubinstein
C
C
Féray
M A
MA
Petit
D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D004279:DNA, Viral; D004797:Enzyme-Linked Immunosorbent Assay; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D016753:Interleukin-10; D011493:Protein Kinase C