Delayed activation of quiescent donor hematopoietic stem cells in the host
marrow cavity by anti-host monoclonal antibody
MW Sadelain and TG Wegmann
Department of Immunology, Faculty of Medicine, University of Alberta,
Edmonton, Canada.
To understand the mechanisms controlling hematopoietic engraftment in
untreated, normal recipients, we investigated the fate of parental, donor
hematopoietic stem cells after apparent graft failures in unconditioned F1
hybrid recipient mice. By administering an anti-host H- 2K monoclonal
antibody, which targets host cells but spares the donor, we found that
chimerism could be induced by delayed conditioning in animals with apparent
graft failure. Engraftment kinetics in the host were followed by typing
individual colony forming unit-- granulocyte/macrophage (CFU-GM) colonies
for their origin and showed that parental cells, which were otherwise
virtually absent, become promptly detectable within the marrow cavity after
antibody administration. Marrow transfers to secondary hosts suggested that
parental stem cells were present in the marrow of the untreated recipients.
These findings establish that the elimination of all parental cells cannot
account for the absence of peripheral blood chimerism in the unconditioned
F1 hybrid recipient. Thus, viable and functional donor stem cells, which
remain quiescent in the host marrow, can be activated by a selective
conditioning regimen and can rescue an apparent graft failure. The
selective activation in vivo of marked stem cells in an unirradiated
microenvironment may be a useful system to study the regulation of cellular
proliferation within the marrow cavity.
Volume 74,
Issue 7,
pp. 2325-2329,
11/15/1989
Copyright © 1989 by The American Society of Hematology
