Despite decades of research, the induction and maintenance of long-term allograft tolerance without immunosuppression remains an elusive goal in the field of solid organ and cell transplantation. Immunosuppressive medications frequently prevent or minimize acute cellular rejection but have failed to halt antidonor antibody production and chronic organ rejection. Past efforts aimed at promoting lasting allograft tolerance have focused primarily on peripheral T-cell depletion, augmentation of regulatory T cells, or induction via simultaneous hematopoietic stem cell transplantation and facilitation of donor chimerism. So far, none of these methods have led to consistently safe, feasible and long lasting donor organ acceptance. Over the course of the past 4 decades, the study of a unique population of antigen-presenting cells known as dendritic cells has shown promise for breaking new ground in achieving indefinite allograft survival without immunosuppression and its associated adverse effects. In this review, we discuss the discovery and early investigations of dendritic cells and chronicle some of the key studies demonstrating their role in transplantation, particularly in indirect allorecognition, the immunologic pathway thought to drive chronic rejection and perhaps tolerance induction.
In this paper the authors report on the role of dendritic cells in allograft rejection and tolerance. Particularly they highlight key studies demonstrating the importance of indirect allorecognition, the immunologic pathway thought to drive chronic rejection and tolerance induction.
1 Department of Surgery, Columbia University Medical Center, New York, NY.
2 Department of Medicine, Columbia University Medical Center, New York, NY.
Received 14 August 2017. Revision received 11 January 2018.
Accepted 14 January 2018.
The authors declare no conflicts of interest.
Funding for this work was provided by the National Institutes for Health 2T32HL007854-21.
S.J.R., P.E.H., and M.A.H. participated in the writing of the article.
Correspondence: Sarah J. Rosen, MD, Rm. 10-502, 630W. 168th St., New York, NY 10032. (firstname.lastname@example.org).