Human airway epithelial cells present antigen to influenza virus-specific CD8+ CTL inefficiently after incubation with viral protein together with ISCOMATRIX.

In the present paper, an in vitro model was established in which the interaction between influenza virus-specific CD8+ T cells and human airway epithelial cells can be studied. To this end, the human lung epithelial cell line A549 was transduced with the HLA-A*0201 gene. This MHC class I allele is involved in the presentation of the immunodominant M158-66 cytotoxic T lymphocyte (CTL) epitope of the influenza A virus matrix protein. The A549-HLA-A2 cells and a CD8+ T cell clone specific for the M158-66 epitope were used to evaluate ISCOMATRIX (IMX), which is considered a potential mucosal adjuvant for influenza vaccines, for its capacity to activate virus-specific CTL after incubation with epithelial cells. It was found that virus infected epithelial cells activated virus-specific CTL efficiently. However, incubation of epithelial cells with ISCOMATRIX and recombinant M1 protein activated CD8+ T cells inefficiently, unlike the incubation of C1R cells expressing a HLA-A2 trans gene or HLA-A2+ B-lymphoblastoid cells with these reagents. It was concluded that this lack of antigen presentation by epithelial cells indicate that these cells are not subject to killing by virus-specific CTL upon instillation with ISCOMATRIX-based vaccines, which may be a favorable property of mucosal vaccines.

In vitro effect of bioactive compounds on influenza virus specific B- and T-cell responses.

In vitro studies have demonstrated positive effects of bioactive compounds on several functions of the immune system. In the present study, 25 of such compounds were tested for their immune modulating properties on influenza virus specific human B- and T-cell responses in vitro. One of these compounds, N-acetyl-L-cysteine was shown to increase influenza virus specific lymphocyte proliferation and interferon(IFN)-gamma production at a concentration of 1.0 mmol/l. Furthermore, N-acetyl-L-cysteine was found to enhance a specific activity of two influenza specific CD8+ cytotoxic T-lymphocyte clones directed towards HLA-A*0201 and HLA-B*2705 restricted epitopes. A second compound, chlorogenic acid, was shown to enhance antigen specific proliferation of lymphocytes in three out of four donors, at concentrations of 10-50 micromol/l. Neither of the two compounds exhibited a positive effect on the production of influenza virus specific antibodies by human peripheral blood mononuclear cells in vitro.