Comparison of allergen-stimulated dendritic cells from atopic and nonatopic donors dissecting their effect on autologous naive and memory T helper cells of such donors

Abstract

Background: Because of their production of IL-12, mature dendritic cells (DC) are potent inducers of TH1 responses. However, recent reports have demonstrated that DCs can also induce TH2 differentiation. Objective: In the current study we investigated which immune response is induced by DCs in naive CD45RA+ or memory CD45R0+ CD4+ T cells from atopic individuals (patients with grass pollen, birch pollen, or house dust mite allergy) compared with nonatopic control subjects. Methods: Immature DCs, generated from peripheral blood monocytes from atopic and nonatopic donors, were pulsed with the respective allergen and fully matured. Then the mature DCs were cocultured in vitro with autologous naive (CD45RA+) and memory (CD45R0+) CD4+ T cells and cytokine and IgE production were measured by ELISA. Results: After the second restimulation with allergen-pulsed DCs, naive as well as memory autologous CD4+ T cells from atopic but not from nonatopic donors showed an enhanced production of the TH2-type cytokines IL-4, IL-5, and IL-10, resulting in an increased IgE production, whereas IFN-γ production and proliferation were not different. IL-12 production and surface marker expression of DCs derived from atopic and nonatopic donors did not differ and addition of neutralizing anti-IL-12 mAbs did not increase IL-4 but diminished IFN-γ production. Conclusion: These data indicate that mature DCs are able to induce naive and activate allergen-specific T helper cells to produce TH2 cytokines if the T cells are derived from atopic donors. This phenomenon is not due to diminished IL-12 production by DCs of atopic donors. (J Allergy Clin Immunol 2000;105:988-96.)