IL-13 PRODUCTION BY ALLERGEN-STIMULATED T-CELLS IS INCREASED IN ALLERGIC DISEASE AND ASSOCIATED WITH IL-S 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 al lergen-driven T-cell responses remains poorly defined. We hypothesized that allergen stimulation of peripheral blood T cells from patients w ith atopic disease compared with non-atopic controls results in elevat ed IL-13 synthesis in the context of a 'Th2-type' pattern. Freshly iso lated peripheral blood mononuclear cells (PBMC) obtained from sensitiz ed atopic patients with allergic disease, and non-atopic control subje cts, were cultured with the allergens Phleum pratense (Timothy grass p ollen) 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-gamma (IFN-gamma) (Th2- and Th1-type cytokines, respe ctively) were determined by enzyme-linked immunosorbent assay (ELISA). Allergen-induced IL-13 and IL-5 production by T cells from patients w ith allergic disease was markedly elevated (P=0.0075 and P=0.0004, res pectively) compared with non-atopic controls, whereas IFN-gamma produc tion was not significantly different. In contrast to allergen, the pro totypic Th1-type antigen M. tuberculosis PPD induced an excess of IFN- gamma over IL-13 and IL-5 production, and absolute concentrations of c ytokines were not affected by the presence or absence of atopic diseas e. Addition of exogenous recombinant IFN-gamma or IL-12, cytokines kno wn to inhibit Th2-type responses, significantly inhibited allergen-dri ven production of both IL-13 and IL-5, but not T-cell proliferation, w hereas exogenous IL-4 did not significantly affect production of IL-13 or IL-5. We conclude that allergen-specific T cells from atopic subje cts secrete elevated quantities of IL-13 compared with non-atopic cont rols, in the context of a Th2-type pattern of cytokine production.