IL-5 secretion by allergen-stimulated CD4+ T cells in primary culture: Relationship to expression of allergic disease

Background: IL-5-producing allergen-specific T cells are thought to play a prominent role in the pathogenesis of allergic inflammation. We hypothesized that T cell allergen-driven IL-5 synthesis is elevated in patients with atopic disease as compared with that in atopic patients free of disease and nonatopic control subjects. Objectives: The purpose of this study was to compare IL-5 and Interferon-γ (IFN-γ) secretion and proliferation by peripheral blood T cells from sensitized atopic patients with asthma, rhinitis, and no symptoms and from nonatopic control subjects in response to the allergen Dermatophagoides pteronyssinus (Der p) and the control recall antigen Mycobacterium tuberculosis purified protein derivative (PPD). Methods: To measure allergen-induced IL-5 production and proliferation, we developed a short-term culture technique that required a single antigenic stimulation of freshly isolated peripheral blood mononuclear cells (PBMC). With this technique, we measured Der p- and PPD-induced IL-5 production and proliferation in PBMC from atopic patients with asthma who were allergic to Der p, atopic patients with rhinitis, atopic patients with no symptoms, and a group of nonatopic normal control subjects. In four experiments, CD4+ or CD8+ T cells were depleted from PBMC to confirm that IL-5 synthesis was T cell dependent. Results: T cell IL-5 production, but not IFN-γ production, in response to Der p was elevated in atopic patients with asthma and atopic patients with rhinitis compared with findings in atopic patients with no symptoms or nonatopic control subjects. IL-5 production was abrogated by depletion of CD4+, but not CD8+, T cells. In subjects with asthma, allergen- driven IL-5 production correlated with bronchial hyperreactivity. Allergen- induced proliferation was also higher in patients with asthma than in atopic subjects with no symptoms or nonatopic controls. T cell IL-5 and IFN-γ production and proliferation in response to PPD were similar regardless of atopic status or disease. Conclusions: Elevated IL-5 production is a characteristic of allergen-specific peripheral blood CD4+ T cells from sensitized patients with atopic disease but not atopy per se.