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Blood, 1 July 2001, Vol. 98, No. 1, pp. 224-230
TRANSPLANTATION
Intravenous injection of apoptotic leukocytes enhances bone
marrow engraftment across major histocompatibility barriers
Marcelo de Carvalho Bittencourt,
Sylvain Perruche,
Emmanuel Contassot,
Stéphanie Fresnay,
Marie-Hélène Baron,
Régis Angonin,
François Aubin,
Patrick Hervé,
Pierre Tiberghien, and
Philippe Saas
From the Etablissement Français du Sang Bourgogne
Franche-Comté, UPRES EA2284-Université de
Franche-Comté, INSERM EO119 Besançon, France; Service
d'Anatomie Pathologique, CHU Besançon, France; Service de
Radiothérapie, CHU Besançon, France; and UPRES EA2085,
IETG, Université de Franche-Comté, Besançon, France.
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.
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