title: Regulation of rat and human T-cell immune response by pharmacologically modified dendritic cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Immunoregulation Laboratory, MRC Centre of Transplantation DIIID, King's College London, Guy's Campus, London, United Kingdom.
authors.forename: Henrieta
authors.initials: H
authors.lastname: Fazekasova
authors.forename: Dela
authors.initials: D
authors.lastname: Golshayan
authors.forename: Joseph
authors.initials: J
authors.lastname: Read
authors.forename: Aristotle
authors.initials: A
authors.lastname: Tsallios
authors.forename: Julia Yuen-Shan
authors.initials: JY
authors.lastname: Tsang
authors.forename: Anthony
authors.initials: A
authors.lastname: Dorling
authors.forename: Andrew J T
authors.initials: AJ
authors.lastname: George
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mirenda
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D015704:CD4 Antigens / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D055633:Immune System Phenomena / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D003907:Dexamethasone