Abstract
Background Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells
with tolerogenic function. The ability of DCs to regulate alloantigen-specific T cell
responses and to promote tolerance has aligned them ideally for a role in vascularized
composite allotransplantation (VCA). In this study, we summarize the current evidence
for DC therapies for tolerance induction to alleviate the requirement for chronic
immunosuppression.
Method A comprehensive and structured review of manuscripts published on VCA was performed
using the MEDLINE and PubMed databases. All eligible studies published from the year
2000 to 2017 were included in the final results.
Result Nineteen original preclinical and clinical studies that employed cell therapy for
VCA were included in this review. In vivo DC therapy was found to direct the alloimmune
response toward either transplant rejection or tolerance in VCA models. While injection
of mature DCs rapidly increases T-cell activity in humans and promotes transplant
rejection, the injection of immature DCs acts as an immunosuppressant and inhibits
T-cell activity. In addition to immature DCs, mesenchymal stem cells were also found
to have a positive effect on allotransplantation of solid organs and bone marrow via
cytokine expression which decreases the alloreactive effector lymphocytes and increases
CD4+/CD25+/FoxP3 Tregs. Despite the promising findings, the efficacy of cell-based
therapies varies greatly across studies, partly due to different methods of cell isolation
and purification techniques, source, route and timing of administration, and combination
immunosuppressive therapy.
Conclusion Additional research is needed to evaluate the efficacy and safety of DC and other
cell-based therapeutic measures in human allotransplant recipients. Future direction
will focus on the development of novel methods to reduce immunosuppression and develop
more individualized management, as well as the clinical application of basic research
in the mechanisms of immunologic tolerance.
Keywords
tolerogenic dendritic cells - dendritic cells - composite tissue allotransplantation
- vascularized composite allotransplantation - immunosuppressive - cell-based therapy
- immune tolerance - transplantation - immature DCs - DCs
