Transient exposure of dendritic cells to maturation stimuli is sufficient to induce complete phenotypic maturation while preserving their capacity to respond to subsequent restimulation.
Dendritic cells (DC) are activated by pathogens, cytokines and activated T cells. We investigated the impact of a transient initial DC stimulation on the kinetics of maturation using a combination of double-stranded RNA and TNFalpha and subsequent restimulation by T cell-derived stimuli. Transient stimulation of DC was sufficient to start an irreversible program of phenotypic maturation which proceeded in the absence of the initial stimulus. Transiently stimulated DC secreted lower amounts of IL-12 during the 48-h period of the first stimulation than cells activated for 48 h. Although both DC preparations expressed the same level of maturation-associated markers at 48 h, DC stimulated for shorter periods preserved higher sensitivity to boosting upon subsequent stimulation by T cell-derived signals. We showed that DC initially stimulated for shorter periods were more potent stimulators of T lymphocytes and they induced a more polarized Th1 response. These results indicate that short exposure of DC to maturation stimuli enables an efficient defensive immune response induction by differentially regulating phenotypic maturation and cytokine production of DC.
Spisek
Radek
R
INSERM U419, Institut de Biologie, 9 Quai Moncousu, 44093, Nantes, France.
Bougras
Gwenola
G
Ebstein
Frederic
F
Masse
Delphine
D
Meflah
Khaled
K
McIlroy
Dorian
D
Gregoire
Marc
M
D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004338:Drug Combinations; D006801:Humans; D016130:Immunophenotyping; D007378:Interleukins / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D004338:Drug Combinations; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D011070:Poly I-C