[Tolerance in transplantation: potential contribution of haematopoietic transplantation and cell therapy].
The ultimate objective of organ transplantation is to obtain a state of tolerance, i.e. long-term acceptance of the graft without immunosuppressive therapy in order to limit the complications of these treatments (viral infections, tumours, etc.). The various immunological mechanisms allowing a state of tolerance will be described in this review. Among these various experimental strategies, combined bone marrow (or haematopoietic stem cell) transplantation and organ transplantation, made possible by the development of non-myeloablative or less intensive conditioning, appears to be one of the most promising lines of research. This approach leads to colonization of the recipient by donor cells. This state is described as "macro-chimerism" and achieves a real state of central tolerance in relation to an organ derived from the bone marrow donor. We have shown recently that intravenous injection of apoptotic cells in combination with allogeneic bone marrow cells increases the success rate of bone marrow transplantation. In a model of combined bone marrow/solid organ transplantation, these apoptotic cells induce tolerance limited to the donor's bone marrow cell antigens without inducing auto-immunization. We therefore propose a new approach to cell-based therapy (using the immunomodulating properties of apoptotic cells) to promote the success of haematopoietic stem cell transplantation. This approach can be particularly useful in combined haematopoietic stem cell and organ transplantation in order to induce a state of macro-chimerism.
Kleinclauss
François
F
Laboratoire de Thérapeutique Immuno-moléculaire, INSERM E-0119/UPRES EA 2284, Etablissement Français du Sang Bourgogne/Franche-Comté, Besançon, France. francoiskleinclauss@club-internet.fr
Bittard
Hugues
H
Perruche
Sylvain
S
de Carvalho-Bittencourt
Marcello
M
Chalopin
Jean-Marc
JM
Hervé
Patrick
P
Tiberghien
Pierre
P
Saas
Philippe
P
D000818:Animals; D017209:Apoptosis; D017690:Cell Transplantation; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D014181:Transplantation Immunology