Regulation of Rat and Human T-cell Immune Response by Pharmacologically Modified Dendritic Cells.

Détails

ID Serval
serval:BIB_FA630122647C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Regulation of Rat and Human T-cell Immune Response by Pharmacologically Modified Dendritic Cells.
Périodique
Transplantation
Auteur(s)
Fazekasova H., Golshayan D., Read J., Tsallios A., Tsang J.Y., Dorling A., George A.J., Lechler R.I., Lombardi G., Mirenda V.
ISSN
1534-6080[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
87
Numéro
11
Pages
1617-1628
Langue
anglais
Résumé
BACKGROUND: The central function of dendritic cells (DC) in inducing and preventing immune responses makes them ideal therapeutic targets for the induction of immunologic tolerance. In a rat in vivo model, we showed that dexamethasone-treated DC (Dex-DC) induced indirect pathway-mediated regulation and that CD4+CD25+ T cells were involved in the observed effects. The aim of the present study was to investigate the mechanisms underlying the acquired immunoregulatory properties of Dex-DC in the rat and human experimental systems. METHODS: After treatment with dexamethasone (Dex), the immunogenicity of Dex-DC was analyzed in T-cell proliferation and two-step hyporesponsiveness induction assays. After carboxyfluorescein diacetate succinimidyl ester labeling, CD4+CD25+ regulatory T-cell expansion was analyzed by flow cytometry, and cytokine secretion was measured by ELISA. RESULTS: In this study, we demonstrate in vitro that rat Dex-DC induced selective expansion of CD4+CD25+ regulatory T cells, which were responsible for alloantigen-specific hyporesponsiveness. The induction of regulatory T-cell division by rat Dex-DC was due to secretion of interleukin (IL)-2 by DC. Similarly, in human studies, monocyte-derived Dex-DC were also poorly immunogenic, were able to induce T-cell anergy in vitro, and expand a population of T cells with regulatory functions. This was accompanied by a change in the cytokine profile in DC and T cells in favor of IL-10. CONCLUSION: These data suggest that Dex-DC induced tolerance by different mechanisms in the two systems studied. Both rat and human Dex-DC were able to induce and expand regulatory T cells, which occurred in an IL-2 dependent manner in the rat system.
Mots-clé
Animals, Antigens, CD4/drug effects, Antigens, CD4/immunology, Bone Marrow Cells/immunology, Cytokines/immunology, Cytokines/secretion, Dendritic Cells/drug effects, Dendritic Cells/immunology, Dexamethasone/pharmacology, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immune System Processes/immunology, Immune Tolerance/drug effects, Immune Tolerance/immunology, Lymph Nodes/immunology, Lymphocyte Culture Test, Mixed, Rats, Rats, Inbred BN, Rats, Inbred Lew, Spleen/immunology, T-Lymphocytes/immunology, T-Lymphocytes, Regulatory/drug effects, T-Lymphocytes, Regulatory/immunology
Pubmed
Web of science
Création de la notice
09/02/2010 12:16
Dernière modification de la notice
03/03/2018 22:55
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