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Current Opinion in Organ Transplantation:
doi: 10.1097/MOT.0000000000000097
TOLERANCE INDUCTION: Edited by Herman Waldmann

Orchestration of transplantation tolerance by regulatory dendritic cell therapy or in-situ targeting of dendritic cells

Morelli, Adrian E.a,b; Thomson, Angus W.a,b

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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.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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