http://repub.eur.nl/res/aut/7902/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/3850/ 2002-03-25T00:00:00Z 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. http://repub.eur.nl/res/pub/9812/ 2002-01-01T00:00:00Z The repertoire of human cytotoxic T-lymphocytes (CTL) in response to influenza A viruses has been shown to be directed towards multiple epitopes, with a dominant response to the HLA-A2-restricted M1(58-66) epitope. These studies, however, were performed with peripheral blood mononuclear cells (PBMC) of individuals selected randomly with respect to HLA phenotype or selected for the expression of one HLA allele without considering an influence of other HLA molecules. In addition, little information is available on the influence of HLA makeup on the overall CTL response against influenza viruses. Here, the influenza A virus-specific CTL response was investigated in groups of HLA-A and -B identical individuals. Between groups the individuals shared two or three of the four HLA-A and -B alleles. After in vitro stimulation of PBMC with influenza virus, the highest CTL activity was found in HLA-A2(+) donors. A similar pattern was observed for the precursor frequency of virus-specific CTL (CTLp) ex vivo, with a higher CTLp frequency in HLA-A2-positive donors than in HLA-A2-negative donors, which were unable to recognize the immunodominant M1(58-66) epitope. In addition, CTL activity and frequency of CTLp for the individual influenza virus epitopes were determined. The frequency of CTLp specific for the HLA-B8-restricted epitope NP(380-388) was threefold lower in HLA-B27-positive donors than in HLA-B27-negative donors. In addition, the frequency of CTLp specific for the HLA-A1-restricted epitope NP(44-52) was threefold higher in HLA-A1-, -A2-, -B8-, and -B35-positive donors than in other donors, which was confirmed by measuring the CTL activity in vitro. These findings indicate that the epitope specificity of the CTL response is related to the phenotype of the other HLA molecules. Furthermore, the magnitude of the influenza virus-specific CTL response seems dependent on the HLA-A and -B phenotypes. http://repub.eur.nl/res/pub/9846/ 2002-01-01T00:00:00Z Here, we describe a new HLA-B*3501-restricted cytotoxic T lymphocyte (CTL) epitope in the influenza A virus (H3N2) nucleoprotein, which was found to exhibit a high degree of variation at nonanchor residues. The influenza virus variants emerged in chronological order, and CTLs directed against old variants failed to recognize more recent strains of influenza A virus, indicating an escape from CTL immunity.