Upregulation of MHC class II antigen on dendritic cells from hepatitis B virus transgenic mice by interferon‐γ: abrogation of immune response defect to a T‐cell‐dependent antigen

Abstract

SUMMARYThe 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, 1 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.1 Immunohistochemical staining has shown that treatment of transgenic mice with mouse recombinant interferon-g (IFN-g), 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-g 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 m g/mouse) could not produce anti-KLH antibodies in sera, but injecting transgenic mice with the same doses of KLH together with IFN-g resulted in the production of anti-KLH antibodies in sera. Again, KLHprimed normal mice-derived T/B lymphocytes produced anti-KLH antibody, when cultured with dendritic cells from IFN-g-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-g 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-g may be used for immune therapy in HBV carriers.

Autocrine, Not Paracrine, Interferon-Gamma Gene Delivery Enhances Ex Vivo Antigen-Specific Cytotoxic T Lymphocyte Stimulation and Killing

“…This was not fully anticipated as IFN- γ affects the phenotype of both DC and T cells. For DC IFN stimulates significantly higher MHC class II, CD86, and slightly higher CD80 levels [ 30 – 32 ]. IFN- γ also stimulates higher IL-12 expression and DC maturation [ 30 – 32 ].…”

Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion

“…IFN-γ directly acts as a cytotoxic CD8 T cell differentiation signal, and it is essential for the induction of cytotoxic T cell precursor proliferation ( 125 , 126 ). IFN-γ also upregulates cell surface MHC class II on APCs, thus promoting peptide-specific activation of CD4 T cells ( 25 , 127 – 129 ). In addition, IFN-γ activates macrophages toward a pro-inflammatory profile, exhibiting an increased phagocytic ability as well as enhanced microbial killing activity ( 130 ).…”

Pathogenesis of Viral Hepatitis-Induced Chronic Liver Disease: Role of Extracellular Vesicles

“…Indeed, the importance of a protective T helper (Th) 1 rather than a tolerant Th2 immune response in clearing HBV has been demonstrated by several studies (Marinos et al, 1995;Maini et al, 2000). Akbar et al demonstrated the importance of IFN-g in controlling HBV infections by showing a reduction in HBV DNA in the liver and sera after dendritic cells were treated with Th1 type cytokine; IFN-g (Akbar et al, 1996). In addition to host immune response, studies have reported the involvement of viral component HBx in the progression of chronic HBV.…”

“…Akbar et al . demonstrated the importance of IFN-γ in controlling HBV infections by showing a reduction in HBV DNA in the liver and sera after dendritic cells were treated with Th1 type cytokine; IFN-γ ( Akbar et al., 1996 ). In addition to host immune response, studies have reported the involvement of viral component HBx in the progression of chronic HBV.…”