Role of T-helper type 2 cytokines in down-modulation of fas mRNA and receptor on the surface of activated CD4(+) T cells: molecular basis for the persistence of the allergic immune response.
The mechanisms responsible for persistence of T lymphocytes at the sites of allergic inflammation are not completely understood. Activated T cells, usually expressing Fas on their surface, undergo activation-induced apoptotic death, thus limiting the dangerous consequences of a persistent immune reaction. We have previously shown that pulmonary T lymphocytes from untreated asthmatic subjects do not express surface Fas receptors nor do they contain Fas mRNA, yet they display normal levels of Fas ligand. This is not an inherited defect and is confined to mucosal T cells. To gain insights into the mechanism responsible for these findings, we performed a set of experiments with both purified Dermatophagoides pteronyssinus allergen and recombinant human cytokines: interleukin 2 (IL-2), IL-4, IL-5, transforming growth factor beta1, interferon gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF). In vitro exposure of purified CD4(+) lymphocytes to allergen yielded only transient up-regulation of surface Fas but did not influence susceptibility to Fas-mediated cell death. T-helper type 2 cytokines (IL-4, IL-5, and GM-CSF) had a dose-dependent and specific inhibitory effect on Fas mRNA, suggesting a new fundamental biological role in the survival of inflammatory cells during allergen exposure.
Spinozzi
F
F
Laboratory of Allergology and Clinical Immunology, Department of Clinical and Experimental Medicine, Perugia, Italy. spinozzi@unipg.it
Agea
E
E
Fizzotti
M
M
Bassotti
G
G
Russano
A
A
Droetto
S
S
Bistoni
O
O
Grignani
F
F
Bertotto
A
A
D000293:Adolescent; D000328:Adult; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016923:Cell Death; D002648:Child; D016207:Cytokines / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D019014:fas Receptor / Q000096:biosynthesis*
D039741:Antigens, Dermatophagoides; D016207:Cytokines; D006023:Glycoproteins; D007378:Interleukins; D018124:Receptors, Tumor Necrosis Factor; D016212:Transforming Growth Factor beta; D019014:fas Receptor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor