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

Background: Because of their production of IL-12, mature dendritic cells (D C) are potent inducers of T(H)1 responses, However recent reports have demo nstrated that DCs can also induce T(H)2 differentiation. Objective: In the current study we investigated which immune response is in duced by DCs in naive CD45RA(+) or memory CD45R0(+) CD4(+) T cells from ato pic individuals (patients with grass pollen, birch pollen, or house dust mi te allergy) compared with nonatopic control subjects. Methods: Immature DCs, generated from peripheral blood monocytes from atopi c 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 pro duction 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 T(H)2-type cytokines IL-4, IL- 5, and IL-10, resulting in an increased IgE production, whereas IFN-gamma p roduction and proliferation were not different. IL-12 production and surfac e 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-gamma production. Conclusion: These data indicate that mature DCs are able to induce naive an d activate allergen-specific T helper cells to produce T(H)2 cytokines if t he T cells are derived from atopic donors. This phenomenon is not due to di minished IL-12 production by DCs of atopic donors.