Specific induction of interleukin-4-producing cells in response to in vitro allergen stimulation in atopic individuals.

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CD4+ T cells can be divided into two major subsets, T helper (TH)1 and TH2 cells. Interleukin-4 (IL-4) is produced by TH2 cells and induces switching of immunoglobulin (Ig) M/IgG to IgE. Interferon-gamma (IFNgamma) produced by TH1 cells counteracts the IgE-promoting effects of IL-4. In this study we wanted to investigate whether the number of IL-4-producing cells could be a direct measurement of allergen exposure in vitro, and whether this was correlated to the elevated serum IgE-levels seen in atopic persons. We compared the number of IL-4- and IFNgamma-producing cells using an enzyme-linked immunospot assay (ELISPOT) in response to allergens from birch and cat in peripheral mononuclear cells from atopic and healthy individuals. In the two sensitized groups there was an increase in the number of IL-4-producing cells in response to the specific allergen which was not seen in the healthy group (1/20000 cells and 1/200000 cells, respectively, P < 0.001 for birch). In criss-cross experiments where birch-sensitized individuals were stimulated with cat allergen, no IL-4-producing cells were seen, indicating a high degree of specificity. In individual subjects, the elevated numbers of IL-4-producing cells were significantly correlated with their allergen-specific serum IgE levels. When allergen was combined with a suboptimal dose of PHA, there was a synergistic increase in the number of allergen-induced IL-4-producing cells (1/4000 cells) in the atopic donors, which was not seen with the number of IFNgamma-producing cells. Allergen-specific IL-4 producing cells in a peripheral blood mononuclear cell (PBMC) culture can be detected by ELISPOT and the response can synergistically be enhanced by suboptimal concentrations of PHA.