IFN-γ inhibits the proliferation of allergen-activated T lymphocytes from atopic, asthmatic patients by inducing Fas/FasL-mediated apoptosis

The defect in interferon‐γ (IFN‐γ) production that results in a T helper cell type 2‐dominated response may be responsible for a decrease in the apoptosis of allergen‐activated T cells in asthma. We investigated the effect of recombinant IFN‐γ on proliferation, Fas/Fas ligand (FasL) expression, and apoptosis in allergen‐stimulated peripheral blood mononuclear cells obtained from atopic, asthmatic patients and nonatopic, control subjects. The addition of IFN‐γ at the start of cultures markedly inhibited the proliferative response to a specific allergen in cells from all asthmatic patients, whereas no change was observed in cells from nonatopic, control subjects. IFN‐γ induced an increase in the expression of Fas and FasL by allergen‐stimulated CD4+ T cells from asthmatic patients and caused the apoptosis of these cells. A Fas‐blocking monoclonal antibody prevented the inhibitory effect of IFN‐γ on allergen‐induced proliferation. These results suggest that IFN‐γ inhibits the proliferation of allergen‐stimulated CD4+ T cells from atopic, asthmatic patients by inducing the surface expression of Fas and FasL, which in turn triggers their apoptotic program. The defect in IFN‐γ production involved in the allergic, immune response may therefore be responsible for a decrease in apoptosis of allergen‐activated T lymphocytes in the airways of atopic, asthmatic patients.