Upregulation of MHC class II antigen on dendritic cells from hepatitis B virus transgenic mice by interferon-gamma: abrogation of immune response defect to a T-cell-dependent antigen.
The experiments presented here were performed to see whether the level of expression of major histocompatibility complex (MHC) class II antigen (Ia antigen) on dendritic cells, one of the most critical antigen presenting cells (APC), influences the humoral immune response in hepatitis B virus (HBV) transgenic mice. We have reported that transgenic mice had a low responsiveness in specific antibody production to keyhole limpet haemocyanin (KLH), a T-cell dependent, HBV-unrelated antigen compared with the age, sex, and major histocompatibility-matched normal mice, due to a significantly lower T-cell stimulatory capacity of transgenic mice-derived dendritic cells, possibly as a result of significantly lower level of Ia antigen. Immunohistochemical staining has shown that treatment of transgenic mice with mouse recombinant interferon-gamma (IFN-gamma), daily for six consecutive days resulted in an increased expression of Ia antigen on splenic dendritic cells. Again, flow cytometric analyses have further confirmed the significant increase in the expression of Ia antigen on dendritic cells, isolated from transgenic mice treated with IFN-gamma compared with the same from the untreated or phosphate-buffered saline (PBS)-treated transgenic mice. Transgenic mice immunized with two optimum doses of KLH (5 micrograms/mouse) could not produce anti-KLH antibodies in sera, but injecting transgenic mice with the same doses of KLH together with IFN-gamma resulted in the production of anti-KLH antibodies in sera. Again, KLH-primed normal mice-derived T/B lymphocytes produced anti-KLH antibody, when cultured with dendritic cells from IFN-gamma-treated transgenic mice expressing a higher level of Ia antigen, but not with the same from PBS-treated or untreated transgenic mice. Treatment of transgenic mice with IFN-gamma resulted in a reduced level of hepatitis B virus (HBV) DNA in liver and in sera. These experiments have shown that the level of expression of Ia antigen on dendritic cells is a critical factor for its APC capability and its modulation of IFN-gamma may be used for immune therapy in HBV carriers.
Akbar
S M
SM
Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
Inaba
K
K
Onji
M
M
D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation / Q000276:immunology; D001483:Base Sequence; D002353:Carrier State / Q000276:immunology*; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology* / Q000628:therapy; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000276:immunology / Q000627:therapeutic use; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D015854:Up-Regulation / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin