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

Background And Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.