Adrian E Morelli1, Angus W Thomson. 1. aDepartment of Surgery, Starzl Transplantation Institute bDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Abstract
PURPOSE OF REVIEW: Extensive research in murine transplant models over the past two decades has convincingly demonstrated the ability of regulatory dendritic cells (DCregs) to promote long-term allograft survival. We review important considerations regarding the source of therapeutic DCregs (donor or recipient) and their mode of action, in-situ targeting of DCregs, and optimal therapeutic regimens to promote DCreg function. RECENT FINDINGS: Recent studies have defined protocols and mechanisms whereby ex-vivo-generated DCregs of donor or recipient origin subvert allogeneic T-cell responses and promote long-term organ transplant survival. Particular interest has focused on how donor antigen is acquired, processed and presented by autologous dendritic cells, on the stability of DCregs, and on in-situ targeting of dendritic cells to promote their tolerogenic function. New evidence of the therapeutic efficacy of DCregs in a clinically relevant nonhuman primate organ transplant model and production of clinical grade DCregs support early evaluation of DCreg therapy in human graft recipients. SUMMARY: We discuss strategies currently used to promote dendritic cell tolerogenicity, including DCreg therapy and in-situ targeting of dendritic cells, with a view to improved understanding of underlying mechanisms and identification of the most promising strategies for therapeutic application.
PURPOSE OF REVIEW: Extensive research in murine transplant models over the past two decades has convincingly demonstrated the ability of regulatory dendritic cells (DCregs) to promote long-term allograft survival. We review important considerations regarding the source of therapeutic DCregs (donor or recipient) and their mode of action, in-situ targeting of DCregs, and optimal therapeutic regimens to promote DCreg function. RECENT FINDINGS: Recent studies have defined protocols and mechanisms whereby ex-vivo-generated DCregs of donor or recipient origin subvert allogeneic T-cell responses and promote long-term organ transplant survival. Particular interest has focused on how donor antigen is acquired, processed and presented by autologous dendritic cells, on the stability of DCregs, and on in-situ targeting of dendritic cells to promote their tolerogenic function. New evidence of the therapeutic efficacy of DCregs in a clinically relevant nonhuman primate organ transplant model and production of clinical grade DCregs support early evaluation of DCreg therapy in human graft recipients. SUMMARY: We discuss strategies currently used to promote dendritic cell tolerogenicity, including DCreg therapy and in-situ targeting of dendritic cells, with a view to improved understanding of underlying mechanisms and identification of the most promising strategies for therapeutic application.
Authors: Z Wang; A T Larregina; W J Shufesky; M J Perone; A Montecalvo; A F Zahorchak; A W Thomson; A E Morelli Journal: Am J Transplant Date: 2006-06 Impact factor: 8.086
Authors: M Segovia; C Louvet; P Charnet; A Savina; G Tilly; L Gautreau; L Carretero-Iglesia; G Beriou; I Cebrian; T Cens; L Hepburn; E Chiffoleau; R A Floto; I Anegon; S Amigorena; M Hill; M C Cuturi Journal: Am J Transplant Date: 2014-04-14 Impact factor: 8.086
Authors: M B Ezzelarab; D Raich-Regue; L Lu; A F Zahorchak; A Perez-Gutierrez; A Humar; M Wijkstrom; M Minervini; R W Wiseman; D K C Cooper; A E Morelli; A W Thomson Journal: Am J Transplant Date: 2017-02-02 Impact factor: 8.086
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