Alison Kay

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-gamma (IFN-gamma) 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-gamma 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-gamma 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.

IL-13 production by allergen-stimulated T cells is increased in allergic disease and associated with IL-5 but not IFN-gamma expression.

Interleukin‐13 (IL‐13) shares many, but not all, of the properties of the prototypic T‐helper type 2 (Th2) cytokine IL‐4, but its role in allergen‐driven T‐cell responses remains poorly defined. We hypothesized that allergen stimulation of peripheral blood T cells from patients with atopic disease compared with non‐atopic controls results in elevated IL‐13 synthesis in the context of a ‘Th2‐type’ pattern. Freshly isolated peripheral blood mononuclear cells (PBMC) obtained from sensitized atopic patients with allergic disease, and non‐atopic control subjects, were cultured with the allergens Phleum pratense (Timothy grass pollen) or Dermatophagoides pteronyssinus (house dust mite) and the non‐allergenic recall antigen Mycobacterium tuberculosis purified protein derivative (PPD). Supernatant concentrations of IL‐13, along with IL‐5 and interferon‐γ (IFN‐γ) (Th2‐ and Th1‐type cytokines, respectively) were determined by enzyme‐linked immunosorbent assay (ELISA). Allergen‐induced IL‐13 and IL‐5 production by T cells from patients with allergic disease was markedly elevated (P=0·0075 and P=0·0004, respectively) compared with non‐atopic controls, whereas IFN‐γ production was not significantly different. In contrast to allergen, the prototypic Th1‐type antigen M. tuberculosis PPD induced an excess of IFN‐γ over IL‐13 and IL‐5 production, and absolute concentrations of cytokines were not affected by the presence or absence of atopic disease. Addition of exogenous recombinant IFN‐γ or IL‐12, cytokines known to inhibit Th2‐type responses, significantly inhibited allergen‐driven production of both IL‐13 and IL‐5, but not T‐cell proliferation, whereas exogenous IL‐4 did not significantly affect production of IL‐13 or IL‐5. We conclude that allergen‐specific T cells from atopic subjects secrete elevated quantities of IL‐13 compared with non‐atopic controls, in the context of a Th2‐type pattern of cytokine production.

The topical glucocorticoids beclomethasone dipropionate and fluticasone propionate inhibit human T-cell allergen-induced production of IL-5, IL-3 and GM-CSF mRNA and protein.

T‐cell production of eosinophil‐active cytokines (IL‐5, IL‐3, GM‐CSF) is thought to be fundamental to asthma pathogenesis. Inhaled aeroallergens may be one important stimulus for T‐cell cytokine production in asthma.