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 r esponses as well as T(H)2 responses. Objective: In this study, we examined the effect of anti-inflammatory agent s such as IL-10 and hydrocortisone (HC) on the accessory function of DCs an d 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 cu lture 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 secr etion. Consequently, T-cell proliferation was reduced after stimulation wit h IL-10- or HC-treated DCs alike. However, pretreatment of DCs with IL-10 i nhibited 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 rel ease of IL-4 and no change in IL-5. Both effects were long-lasting; cytokin e production remained low (which was due not to enhanced. hyporesponsivenes s) or even apoptosis but to functional hy increased after restimulation wit h fully matured DCs. Conclusion: These data indicate that IL-10- or HC-treated DCs differ in the ir ability to influence human allergic T-cell responses. This has major imp lications for therapeutic strategies. aiming at the downregulation of proal lergic T(H)2 responses.