Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalo-Universitaire Chenevier Mondor, Centre d'Investigation Clinique Biothérapie, Créteil, France.
Institut Mondor de recherche biomédicale, Université Paris-Est, UMR_S955, UPEC, Créteil, France.
Front Immunol. 2019 Dec 18;10:2908. doi: 10.3389/fimmu.2019.02908. eCollection 2019.
The induction of specific and sustainable tolerance is a challenging issue in organ transplantation. The discovery of the immunosuppressive properties of apoptotic cells in animal models has paved the way for their use in human transplantation. In this work, we aimed to define a stable, reproducible, and clinically compatible production procedure of human apoptotic cells (Apo-cells). Using a clinically approved extracorporeal photopheresis technique, we have produced and characterized phenotypically and functionally human apoptotic cells. These Apo-cells have immunosuppressive properties proved and in NOD/SCID/γC mice by their capacity to modulate an allogeneic response following both a direct and an indirect antigen presentation. These results brought the rationale for the use of Apo-cells in tolerance induction protocol for organ transplantation.
诱导特异性和可持续性耐受是器官移植中的一个挑战。在动物模型中发现凋亡细胞具有免疫抑制特性,为其在人类移植中的应用铺平了道路。在这项工作中,我们旨在定义一种稳定、可重复和临床兼容的人凋亡细胞(Apo-cells)生产程序。使用临床批准的体外光化学疗法,我们已经生产并表征了表型和功能上的人凋亡细胞。这些 Apo-cells 具有免疫抑制特性,通过其在直接和间接抗原呈递后调节同种异体反应的能力在 NOD/SCID/γC 小鼠中得到证实。这些结果为在器官移植的诱导耐受方案中使用 Apo-cells 提供了依据。