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

Cross-tolerization of T lymphocytes after apoptotic cell uptake by dendriti c cells may be involved in self-tolerance maintenance. Furthermore, immunos uppressive properties are attributed to apoptotic cells, This study evaluat ed the consequences of apoptotic leukocyte administration in a restrictive engraftment model of murine bone marrow (BM) transplantation. Sublethally i rradiated recipients received a limited number of allogeneic BM, with or wi thout 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, ind ependently of the origin (donor,recipient, third-party mice, as well as xen ogeneic peripheral blood mononuclear cells), significantly enhanced engraft ment, Similar results were obtained after infusion of leukocytes rendered a poptotic by UVB irradiation or by anti-Pas monoclonal antibody stimulation, thus confirming the role of apoptotic cells in engraftment facilitation. O verall, these results suggest that apoptotic leukocytes can nonspecifically facilitate allogeneic BM engraftment, Such a simple approach could he of i nterest in BM transplantation settings involving an important HLA donor/rec ipient disparity, a T-cell-depleted graft, or reduced conditioning regimen intensity. (C) 2001 by The American Society of Hematology.