Dendritic cells, tolerance and transplantation

Dendritic cells (CD) are professional antigen-presenting cells of the immune system that play a central role in the initiation of the alloimmune response. Recently these cells have been found to also play a role in the maintenance of peripheral tolerance to antigens. Dendritic cells initiate alloimmunity by migrating from the graft to lymphoid sites within the host where they activate alloantigen-specific T cells. They are therefore an ideal target for new biological therapies aiming to divert the response away from immunity and towards tolerance. Genetic modification of DC with immunosuppressive cytokines has already proven successful in modifying the alloimmune response in vitro and in prolonging allograft survival in small animal transplantation studies. Manipulation of the DC subsets that maintain peripheral tolerance and targeting the mechanisms that control DC immunogenicity with somatic gene therapy is a promising and novel means of inducing immunosuppression for transplantation.