Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers.

Fiche publication


Date publication

juillet 2001

Journal

Blood

Auteurs

Membres identifiés du Cancéropôle Est :
Pr AUBIN François, Pr DE CARVALHO BITTENCOURT Marcelo, Dr PERRUCHE Sylvain


Tous les auteurs :
Bittencourt MC, Perruche S, Contassot E, Fresnay S, Baron MH, Angonin R, Aubin F, Hervé P, Tiberghien P, Saas P

Résumé

Cross-tolerization of T lymphocytes after apoptotic cell uptake by dendritic cells may be involved in self-tolerance maintenance. Furthermore, immunosuppressive properties are attributed to apoptotic cells. This study evaluated the consequences of apoptotic leukocyte administration in a restrictive engraftment model of murine bone marrow (BM) transplantation. Sublethally irradiated recipients received a limited number of allogeneic BM, with or without irradiated apoptotic leukocytes of different origins. No graft-versus-host disease was observed. Whereas only a low proportion of mice receiving BM cells alone engrafted, addition of apoptotic irradiated leukocytes, independently of the origin (donor, recipient, third-party mice, as well as xenogeneic peripheral blood mononuclear cells), significantly enhanced engraftment. Similar results were obtained after infusion of leukocytes rendered apoptotic by UVB irradiation or by anti-Fas monoclonal antibody stimulation, thus confirming the role of apoptotic cells in engraftment facilitation. Overall, these results suggest that apoptotic leukocytes can nonspecifically facilitate allogeneic BM engraftment. Such a simple approach could be of interest in BM transplantation settings involving an important HLA donor/recipient disparity, a T-cell-depleted graft, or reduced conditioning regimen intensity.

Mots clés

Animals, Apoptosis, radiation effects, Bone Marrow Transplantation, methods, Graft Survival, Graft vs Host Disease, prevention & control, Histocompatibility, Injections, Intravenous, Leukocyte Transfusion, methods, Leukocytes, radiation effects, Male, Mice, Mice, Inbred BALB C, Models, Animal, Spleen, cytology, Transplantation, Heterologous, methods, Transplantation, Homologous, methods

Référence

Blood. 2001 Jul;98(1):224-30