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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
09:51

Development and Functional Characterization of Murine Tolerogenic Dendritic Cells

Published on: May 18, 2018

Immature and maturation-resistant human dendritic cells generated from bone marrow require two stimulations to induce

Thomas G Berger1, Hendrik Schulze-Koops, Michaela Schäfer

  • 1Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.

Plos One
|August 15, 2009
PubMed

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.

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