Negative vaccination by tolerogenic dendritic cells in organ transplantation
- 1 December 2010
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Organ Transplantation
- Vol. 15 (6), 738-743
- https://doi.org/10.1097/mot.0b013e32833f7114
Abstract
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. 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. 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.Keywords
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