Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers.
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.
Bittencourt
M C
MC
Etablissement Français du Sang Bourgogne Franche-Comté, UPRES EA2284-Université de Franche-Comté, INSERM EO119 Besançon, France.
Perruche
S
S
Contassot
E
E
Fresnay
S
S
Baron
M H
MH
Angonin
R
R
Aubin
F
F
Hervé
P
P
Tiberghien
P
P
Saas
P
P
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D016026:Bone Marrow Transplantation / Q000379:methods*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D006648:Histocompatibility; D007275:Injections, Intravenous; D017708:Leukocyte Transfusion / Q000379:methods*; D007962:Leukocytes / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D013154:Spleen / Q000166:cytology / Q000528:radiation effects; D014183:Transplantation, Heterologous / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods