Dendritic cells and regulation of alloimmune responses: relevance to outcome and therapy of organ transplantation.

Dendritic cells are uniquely well-equipped for antigen capture, processing and presentation. They are highly-efficient antigen-presenting cells that induce and regulate T-cell reactivity. Due to their inherent tolerogenicity, immature dendritic cells offer considerable potential as candidate cellular vaccines for negative regulation of immune reactivity/promotion of tolerance. Both classic myeloid and, more recently, characterized plasmacytoid dendritic cells, exhibit tolerogenic properties. Manipulation of dendritic cells differentiation/ maturation in the laboratory using cytokines, pharmacologic agents or genetic engineering approaches can render stably immature dendritic cells that promote organ transplant tolerance in rodents. There are also indications from human studies of the ability of dendritic cells to promote T-cell tolerance and induce T-regulatory cells, with potential for therapeutic application in organ transplantation. In addition, recent clinical observations suggest that modulation of dendritic cell function (e.g., by immunosuppressive drugs) affects the outcome of transplantation. The challenge confronting applied dendritic cell biology is the identification of optimal strategies and therapeutic regimens to allow the potential of these powerful immune regulatory cells to be realized in the clinic.