title: Immature and maturation-resistant human dendritic cells generated from bone marrow require two stimulations to induce T cell anergy in vitro.
abstract: Immature dendritic cells (DC) represent potential clinical tools for tolerogenic cellular immunotherapy in both transplantation and autoimmunity. A major drawback in vivo is their potential to mature during infections or inflammation, which would convert their tolerogenicity into immunogenicity. The generation of immature DC from human bone marrow (BM) by low doses of GM-CSF (lowGM) in the absence of IL-4 under GMP conditions create DC resistant to maturation, detected by surface marker expression and primary stimulation by allogeneic T cells. This resistence could not be observed for BM-derived DC generated with high doses of GM-CSF plus IL-4 (highGM/4), although both DC types induced primary allogeneic T cell anergy in vitro. The estabishment of the anergic state requires two subsequent stimulations by immature DC. Anergy induction was more profound with lowGM-DC due to their maturation resistance. Together, we show the generation of immature, maturation-resistant lowGM-DC for potential clinical use in transplant rejection and propose a two-step-model of T cell anergy induction by immature DC.
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Berger
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schulze-Koops
authors.forename: Michaela
authors.initials: M
authors.lastname: Schäfer
authors.forename: Ester
authors.initials: E
authors.lastname: Müller
authors.forename: Manfred B
authors.initials: MB
authors.lastname: Lutz
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology*; D017635:Clonal Anergy; D003713:Dendritic Cells / Q000166:cytology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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