title: Immunomodulatory Effects of 1,25-Dihydroxyvitamin D3on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens.
abstract: While emerging evidence indicates that dendritic cells (DC) play a central role in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory agents provides prospect as disease-modifying therapy. Our observations reveal that 1,25-dihydroxyvitamin D3(1,25(OH)2D3) treatment of monocyte-derived DC results in a semimature phenotype and anti-inflammatory cytokine profile as compared to conventional DC, in both healthy controls and MS patients. Importantly, 1,25(OH)2D3-treated DC induce T cell hyporesponsiveness, as demonstrated in an allogeneic mixed leukocyte reaction. Next, following a freeze-thaw cycle, 1,25(OH)2D3-treated immature DC could be recovered with a 78% yield and 75% viability. Cryopreservation did not affect the expression of membrane markers by 1,25(OH)2D3-treated DC nor their capacity to induce T cell hyporesponsiveness. In addition, the T cell hyporesponsiveness induced by 1,25(OH)2D3-treated DC is antigen-specific and robust since T cells retain their capacity to respond to an unrelated antigen and do not reactivate upon rechallenge with fully mature conventional DC, respectively. These observations underline the clinical potential of tolerogenic DC (tolDC) to correct the immunological imbalance in MS. Furthermore, the feasibility to cryopreserve highly potent tolDC will, ultimately, contribute to the large-scale production and the widely applicable use of tolDC.
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Wai-Ping
authors.identifier: 0000-0001-9113-7317
authors.initials: WP
authors.lastname: Lee
authors.affiliation: Department of Neurology, Antwerp University Hospital, 2650 Edegem, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Willekens
authors.affiliation: Department of Neurology, Antwerp University Hospital, 2650 Edegem, Belgium; Department of Neurology, Born Bunge Institute, Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cras
authors.affiliation: Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti and Department of Cell Biology, Physiology and Immunology, The Autonomous University of Barcelona, 08913 Bellaterra, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Martínez-Cáceres
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium; Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, 2650 Edegem, Belgium.
authors.forename: Zwi N
authors.initials: ZN
authors.lastname: Berneman
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Nathalie
authors.identifier: 0000-0002-0459-901X
authors.initials: N
authors.lastname: Cools
mesh_terms: D000328:Adult; D000941:Antigens / Q000276:immunology; D002454:Cell Differentiation; D015925:Cryopreservation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology; D009186:Myelin Sheath / Q000737:chemistry / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000941:Antigens; D016207:Cytokines; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D