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, us ually expressing Fas on their surface, undergo activation-induced apoptotic death, thus limiting the dangerous consequences of a persistent immune rea ction. We have previously shown that pulmonary T lymphocytes from untreated asthmatic subjects do not express surface Fas receptors nor do they contai n Fas mRNA,yet they display normal levels of Fas ligand. This: is not an in herited defect and is confined to mucosal T cells. To gain insights into th e mechanism responsible for these findings, we performed a set of experimen ts with both purified Dermatophagoides pteronyssinus allergen and recombina nt human cytokines: interleukin 2 (IL-2), IL-4, IL-5, transforming growth f actor beta(1), interferon gamma, and granulocyte-macrophage colony-stimulat ing factor (GM-CSF). In vitro exposure of purified CD4(+) lymphocytes to al lergen yielded only transient up-regulation of surface Fas but did not infl uence susceptibility to Fas-mediated cell death. T-helper type 2 cytokines (IL-4, IL-5, and GMCSF) 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.