6533b85cfe1ef96bd12bc94c

RESEARCH PRODUCT

Inhibition of human allergic T-cell responses by IL-10–treated dendritic cells: Differences from hydrocortisone-treated dendritic cells

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Abstract Background: Dendritic cells (DCs) are able to induce human allergic T H 1 responses as well as T H 2 responses. Objective: In this study, we examined the effect of antiinflammatory agents such as IL-10 and hydrocortisone (HC) on the accessory function of DCs and the resulting T-cell response, especially that of T H 2 cells. Methods: Naive and memory CD4 + T cells from atopic donors were stimulated with autologous allergen-pulsed DCs generated from CD14 + monocytes by culture with GM-CSF/IL-4 and fully matured with IL-1β, TNF-α, and PGE 2 in the presence or absence of IL-10 or HC. Results: IL-10–treated DCs and, to a lesser extent, HC-treated DCs showed a decreased expression of MHC II molecules, the costimulatory molecule CD86, and the DC-specific marker CD83, as well as a strongly reduced IL-12 secretion. Consequently, T-cell proliferation was reduced after stimulation with IL-10– or HC-treated DCs alike. However, pretreatment of DCs with IL-10 inhibited the production of T H 1 and T H 2 cytokines by T cells, whereas HC-treated DCs inhibited production of IFN-γ but induced an increased release of IL-4 and no change in IL-5. Both effects were long-lasting; cytokine production remained low (which was due not to enhanced apoptosis but to functional hyporesponsiveness) or even increased after restimulation with fully matured DCs. Conclusion: These data indicate that IL-10– or HC-treated DCs differ in their ability to influence human allergic T-cell responses. This has major implications for therapeutic strategies aiming at the downregulation of proallergic T H 2 responses. (J Allergy Clin Immunol 2001;108:242-9.)