Impaired functional capacities of liver dendritic cells from murine hepatitis B virus (HBV) carriers: relevance to low HBV-specific immune responses.
The chronic hepatitis B virus (HBV) carrier exhibits ongoing replication of HBV and expresses abundant amounts of HBV-related antigens in the liver. However, HBV-specific immune responses are either absent or narrowly focused in these subjects. With the postulation that impaired functional abilities of liver dendritic cells (DCs) might be responsible for this, we assessed the functions of liver DCs in HBV transgenic mice (HBV-TM), an animal model of the HBV carrier state. Liver DCs were isolated from normal C57BL/6 mice and HBV-TM without the use of cytokines or growth factors. Lymphoproliferative assays were conducted to evaluate the ability of liver DCs to induce the proliferation of allogenic T lymphocytes and hepatitis B surface antigen (HBsAg)-enriched T lymphocytes. Liver DCs were stimulated with viral and bacterial products to assess their cytokine-producing capacities. In comparison to liver DCs from normal C57BL/6 mice, liver DCs from HBV-TM exhibited significantly decreased T cell proliferation-inducing capacities in allogenic mixed leucocyte reaction (P <0.05) and HBsAg-enriched T lymphocytes proliferation assays (P <0.05). Liver DCs from HBV-TM produced significantly lower levels of interleukin-12p70, tumour necrosis factor-alpha, interferon-gamma, and interleukin-6 (P <0.05) compared to liver DCs from normal C57BL/6 mice. This study provides evidence that liver DCs from HBV-TM had impaired ability to induce both innate and adaptive immune responses. This might account for a weak and almost undetectable HBV-specific immune response in chronic HBV carriers. This inspires hope that up-regulation of the functions of liver DCs in situ may have therapeutic implications in chronic HBV carriers.
Hasebe
A
A
Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
Akbar
S M F
SM
Furukawa
S
S
Horiike
N
N
Onji
M
M
D000818:Animals; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008099:Liver / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D021122:Protein Subunits / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D006514:Hepatitis B Surface Antigens; D015850:Interleukin-6; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma