Harnessing dendritic cells for the induction of transplantation tolerance.
OBJECTIVE
The unique properties of dendritic cells (DC) lend themselves to the modulation of antigen-specific immune responses, including allograft rejection. Central to their modulatory function is the capacity of DC to polarize naïve T cells towards a regulatory phenotype and to expand existing regulatory T cells (Treg). This review draws on current understanding of the interaction between these critical cell types to evaluate prospects for the use of DC as a therapeutic regimen.


RESULTS
Over the past year, there have been significant developments in dissecting the molecular basis of DC-Treg interactions. Furthermore, it has proven possible to capitalize on this understanding to reinforce tolerance by conditioning DC through exposure to defined pharmacological agents. The use of these modulated DC in animal models of allograft rejection has highlighted the therapeutic potential of this approach but also the full extent of the challenges that remain to be addressed.


CONCLUSIONS
The use of DC to induce antigen-specific tolerance by tapping into the Treg network remains a viable prospect for future strategies for immune intervention in allograft rejection. Furthermore, principles learned from the study of whole organ transplantation may find application in the emerging field of regenerative medicine, in which the use of immune suppression is likely to be contraindicated.
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Kathryn M
KM
Silk
Paul J
PJ
Fairchild
D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D023421:Models, Animal; D016377:Organ Transplantation; D044968:Regenerative Medicine; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents