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Curr Opin Organ Transplant. 2014 Aug;19(4):348-56. doi: 10.1097/MOT.0000000000000097.

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

Author information

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.

PMID:
24926700
PMCID:
PMC4204930
DOI:
10.1097/MOT.0000000000000097
[Indexed for MEDLINE]
Free PMC Article

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