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 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-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 apoptosis but to functional hyporesponsiveness) or even increased after restimulation with fully matured DCs.


CONCLUSIONS
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.
Bellinghausen
I
I
Department of Dermatology, University of Mainz, Germany.
Brand
U
U
Steinbrink
K
K
Enk
A H
AH
Knop
J
J
Saloga
J
J
D000485:Allergens; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects
D000485:Allergens; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D006854:Hydrocortisone