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

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 anti-inflammatory 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-1 beta, TNF-alpha 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-gamma 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. hyporesponsiveness) or even apoptosis but to functional hy 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.