The hepatitis C virus (HCV) induces a long-term increase in interleukin-10 production by human CD4+ T cells (H9)

• Published in: European cytokine network (Montrouge) Vol. 12; no. 1; p. 69
• Main Authors: Delpuech, O, Buffello-Le Guillou, D B, Rubinstein, E, Féray, C, Petit, M A
• Format: Journal Article
• Language: English
• Published: France 01.03.2001
• Subjects: Base Sequence; CD4-Positive T-Lymphocytes - enzymology; CD4-Positive T-Lymphocytes - metabolism; DNA, Viral; Enzyme-Linked Immunosorbent Assay; Hepacivirus - physiology; Humans; Interleukin-10 - biosynthesis; Interleukin-10 - genetics; Phenotype; Polymorphism, Single-Stranded Conformational; Protein Kinase C - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Viral - genetics; Signal Transduction; Tumor Cells, Cultured
• ISSN: 1148-5493

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.