Human autologous tolerogenic dendritic cells impair T-cell proliferation through contact-independent mechanisms

Abstract

International audienceAutologous tolerogenic dendritic cells (ATDC) have been demonstrated to be able to increase heart, skin and pancreatic islet allograft survivals in murine models and to be safe in non human primates. Due to their efficacy and their safety, ATDC therapy has been moved to clinic in a first phase I/II clinical trial in kidney transplantation in the context of the ONE study project. Human ATDC are generated from elutriated monocytes cultured 6 days in AIMV medium supplemented with low dose of GM-CSF. After differentiation ATDC display a tolerogenic dendritic cell profile (i.e. they display an immature phenotype, they express immunomodulatory cytokines such as IL-10 and TGF-β, they are resistant to maturation and they have suppressive activity toward T-cells). This project aims to determine the suppressive mechanisms of human ATDC toward T-cells