IFN-gamma inhibits the proliferation of allergen-activated T lymphocytes from atopic, asthmatic patients by inducing Fas/FasL-mediated apoptosis.
The defect in interferon-gamma (IFN-gamma) 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-gamma 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-gamma 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-gamma 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-gamma on allergen-induced proliferation. These results suggest that IFN-gamma 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-gamma 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.
De Rose
Virginia
V
Respiratory Disease Division, Department of Clinical and Biological Sciences, University of Turin, Italy. virginia.derose@unito.it
Cappello
Paola
P
Sorbello
Valentina
V
Ceccarini
Barbara
B
Gani
Federica
F
Bosticardo
Marita
M
Fassio
Stefania
S
Novelli
Francesco
F
D000485:Allergens / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D001249:Asthma / Q000378:metabolism*; D002455:Cell Division / Q000276:immunology; D053222:Fas Ligand Protein; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D000485:Allergens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D007371:Interferon-gamma