Location, location, location: dendritic cell trafficking and transplant tolerance

Use or targeting of dendritic cells for therapeutic manipulation of immune responses is being pursued in the areas of cancer, autoimmune disease, and allograft rejection. There is, however, a dearth of information regarding the optimal route of cell delivery or target location for maximal therapeutic effect, particularly in the field of transplantation. Further, little attention has been given to the roles that conventional experimental/immunosuppressive modalities have on the migratory capacity of these important antigen-presenting cells.

Current understanding of the role of dendritic cells in immunologic ignorance, graft rejection, or tolerance to alloantigen suggests their function is influenced by subset, secondary lymphoid tissue location, and the type of organ transplanted. It also has been determined recently that dendritic cell subsets probably utilize distinct migratory routes to secondary lymphoid tissues, further underscoring the importance of understanding dendritic cell trafficking for optimization of dendritic cell therapy protocols.

Increased comprehension of the requirements for dendritic cell-T cell interactions to take place in specific secondary lymphoid tissues for the induction of rejection versus tolerance, with and without antirejection therapy, will facilitate the ease with which cell-based therapy can be designed and implemented in transplant recipients.