Impaired Allostimulatory Capacity of Peripheral Blood Dendritic Cells Recovered from Hepatitis C Virus-Infected Individuals

• Published in: The Journal of immunology (1950) 1999-05, Vol.162 (9), p.5584-5591
• Main Authors: Kanto, Tatsuya, Hayashi, Norio, Takehara, Tetsuo, Tatsumi, Tomohide, Kuzushita, Noriyoshi, Ito, Akihiko, Sasaki, Yutaka, Kasahara, Akinori, Hori, Masatsugu
• Format: Article
• Language: English
• Subjects: Adult; Antigen Presentation; Antigens, T-Independent - immunology; Antigens, T-Independent - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Dendritic Cells - classification; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dextrans - analysis; Dextrans - metabolism; Female; Fluorescein-5-isothiocyanate - analogs & derivatives; Fluorescein-5-isothiocyanate - metabolism; Hepacivirus - immunology; Hepatitis C - blood; Hepatitis C - immunology; Hepatitis C virus; Humans; Immunophenotyping; Interferon-gamma - biosynthesis; Interleukin-12 - biosynthesis; Interleukin-12 - genetics; Interleukin-12 - pharmacology; Interleukin-2 - pharmacology; Lipopolysaccharides - pharmacology; Lymphocyte Activation - immunology; Lymphocyte Culture Test, Mixed; Male; Transcription, Genetic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.9.5584

In hepatitis C virus (HCV) infection, Th responses are implicated in the pathogenesis of liver disease. The dendritic cell (DC) is the most potent activator of CD4 T cells for supporting Th1 differentiation. To clarify the roles of DC of HCV-infected individuals in the development of CD4 T cell responses, we generated peripheral DC with GM-CSF and IL-4 from 24 chronic hepatitis C patients and 14 healthy donors. We then compared their potentials for stimulating allogeneic CD4 T cells, autologous CD4 T cells against influenza A or HCV core Ags, and cytokine production. The DC from the patients (HCV-DC) expressed lower degrees of CD86 than DC from the donors (N-DC), whereas no difference was found in the HLA molecules and other costimulators. HCV-DC stimulated allogeneic T cells less than N-DC; however, influenza A- or core-pulsed HCV-DC retained the potentials for autologous T cell proliferation. In allogeneic DC/T cell cultures, the IFN-gamma levels with HCV-DC were lower than those with N-DC, which may be related to the low expressions of IL-12 p35 and p40 transcripts in HCV-DC. The stimulation with LPS disclosed that HCV-DC is less potent in IL-12 p70 production than N-DC. In the autologous cultures, the pulsing of the Ags to HCV-DC increased the IL-12 p40 and IFN-gamma production and up-regulated the transcription of both IL-12 subunits. Exogenous IL-2 or IL-12 restored the low allogeneic T cell proliferation with HCV-DC in a dose-dependent manner. Therefore, low expression of CD86 and/or IL-12 is crucially involved in the low allostimulatory capacity of HCV-DC. Low IL-12 and low IFN-gamma milieu with HCV-DC on encounters with alloantigens may impede Th1 polarization.