Article: article from journal or magazin.
Regulation of Rat and Human T-cell Immune Response by Pharmacologically Modified Dendritic Cells.
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.
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
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