Differential effects of corticosteroids during different stages of dendritic cell maturation.
Dendritic cell (DC) maturation is a complex process involving many cell functions. We have studied how the exposure of DC to corticosteroids at different stages of DC maturation affects priming and the expansion of different subsets of CD4(+) T cells. Growth factor- dependent DC lines and fresh bone marrow-derived DC were used. When exposed to inflammatory stimuli, immature DC previously treated with dexamethasone were unable to undergo full maturation and were unable to prime Th1 cells efficiently. There was specific and significant reduction in the number of IFN-gamma-producing effector cell (shown by intracellular cytokine staining) and also in the amount of IFN-gamma produced. Interestingly, the number of IL-4-producing T cells and the amount of IL-4 synthesis was not significantly altered. Furthermore, multiple restimulation of T cells with these DC gave rise to a subpopulation of T regulatory cells (Tr1) which were negative for IFN-gamma and IL-4 but were IL-10 positive. In contrast, when DC were activated with lipopolysaccharide prior to dexamethasone treatment, the suppressive effect of glucocorticoids was not significant. Thus, the stage of DC maturation influences the inhibitory effect of corticosteroids. By arresting DC maturation, corticosteroids strongly reduce cell-mediated Th1 responses and allow the selective expansion of Tr1 cells.
Matyszak
M K
MK
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy.
Citterio
S
S
Rescigno
M
M
Ricciardi-Castagnoli
P
P
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D008070:Lipopolysaccharides; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma