Negative vaccination by tolerogenic dendritic cells in organ transplantation.
OBJECTIVE
We discussed the use of autologous tolerogenic dendritic cell (Tol-DC) therapy in organ transplantation, with a particular emphasis on illustrating the reasons why it is a clinically relevant approach and interpreting the experimental data that support this strategy.


RESULTS
Various parameters are critical for engineering Tol-DCs as a therapeutic tool to manipulate antigen-specific immune responses. Our group has shown that in rats, mice and nonhuman primates, bone marrow progenitors cultured with low doses of granulocyte macrophage colony-stimulating factor can generate Tol-DCs. Injection of autologous Tol-DCs (the same strain as the recipient) is able to significantly prolong allograft survival. Autologous Tol-DCs are more effective than allogeneic Tol-DCs in prolonging allograft survival. Although the reason of this difference remains unclear, it indicates the practical advantages of autologous Tol-DCs as a therapeutic tool in a clinical setting. When autologous Tol-DCs (not pulsed with donor antigens) are administered along with suboptimal immunosuppression treatment, a synergistic effect is achieved, resulting in donor-specific allograft tolerance.


CONCLUSIONS
Autologous Tol-DC therapy is a promising approach to improve long-term allograft survival. This strategy may also help reduce the immunosuppressive load in grafted patients and, therefore, limit the harmful effects of immunosuppressive agents.
Hill
Marcelo
M
aINSERM U643, France bCHU de Nantes, France cUniversité de Nantes, UMR 643, Nantes, France dFacultad de Medicina, Departamento de Inmunobiologia, Universidad de la Republica, Montevideo, Uruguay.
Cuturi
Maria C
MC
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D006085:Graft Survival / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D051379:Mice; D016377:Organ Transplantation; D011323:Primates; D051381:Rats; D023001:Transplantation Tolerance / Q000276:immunology*; D014182:Transplantation, Autologous; D014611:Vaccination
D007166:Immunosuppressive Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor