Loss of immunogenecity of liver dendritic cells from mouse with chronic hepatitis.
Antigen presenting cells, especially the antigen presenting dendritic cells (DC) in the tissue, regulate the magnitude of antigen-specific immune response. A role of impaired and narrowly focused specific immune response has been implicated in the pathogenesis of chronic hepatitis due to hepatitis B virus and hepatitis C virus. In order to clarify this role, we studied liver DC from interferon gamma (IFN-gamma) transgenic mouse (TgM), an animal model of chronic hepatitis. These mice had high serum levels of alanine transaminase and histological evidence of chronic hepatitis. Transgene negative offspring (littermate control) with normal serum transaminase levels and without any evidence of hepatitis were used as controls. The stimulatory capacity of the liver DC from IFN-gamma TgM in allogenic mixed leukocyte reaction was significantly lower than that of the liver DC from control mouse. The endocytosis capacity was significantly lower in liver DC from IFN-gamma TgM than in that from the control mouse. Most importantly, liver DC from IFN-gamma TgM were unable to induce antigen-specific proliferation. The impaired function of liver DC from these mice may be attributable to increased production or induction of suppressor cytokines such as interleukin-10 and nitric oxide. Defective capacity of liver DC from mouse with chronic hepatitis (IFN-gamma TgM) may be related to impaired magnitude of specific immune response in the liver.
Abe
Masanori
M
Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Toshima-ku, Tokyo 170-8455, Japan.
Kajino
Kazunori
K
Akbar
Sk Md Fazle
SM
Yamamura
Ken-Ichi
K
Onji
Morikazu
M
Hino
Okio
O
D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D004705:Endocytosis; D005434:Flow Cytometry; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006520:Hepatitis, Animal; D006521:Hepatitis, Chronic / Q000209:etiology / Q000276:immunology*; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000096:biosynthesis; D013234:Stem Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D006514:Hepatitis B Surface Antigens; D009569:Nitric Oxide; D007371:Interferon-gamma