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Differential Cytotoxicity of Cord Blood and Bone Marrow-Derived
Natural Killer Cells
Clair M. Gardiner,
Anne O' Meara, and
Denis J. Reen
From The Children's Research Centre, Our Lady's Hospital for Sick
Children, Crumlin, Dublin, Ireland.
Allogeneic cord blood is now being widely used as a source of stem
cells for hematologic reconstitution after myeloablative therapy, with
reported significantly lower levels of graft-versus-host disease (GVHD)
compared with the use of allogeneic bone marrow (BM). This study was
undertaken to investigate biologic aspects of natural killer (NK) cell
activity, as recognized effector cells of the GVHD and
graft-versus-leukemia (GVL) response, from cord blood and conventional
BM. NK-cell activity levels of freshly isolated cells from cord blood
and BM against K562 targets were comparable. Lymphokine activated
killer (LAK) cells from both hematopoietic cell sources were compared
for their ability to kill target cells by necrotic or apoptotic
mechanisms using specific target cell lines. Cord blood cells had
significantly higher necrosis-mediated cytotoxic activity against Daudi
target cells compared with BM-derived cells. Cord blood LAK cells had
relatively high levels of apoptotic-mediated cytotoxicity against YAC-1
target cells, whereas BM-derived LAK cells were unable to induce
apoptosis in these cells. Interleukin-2 (IL-2) induced significant
granzyme B activity in cord cells in contrast to BM cells, in which
very little activity was measured. Western blotting confirmed these
findings, with IL-2 inducing granzyme B protein expression in cord
cells but not detectable levels in BM cells. BM cells had significantly
lower cell surface expression of IL-2R and prolonged culture in IL-2
was only partially able to restore their deficient apoptotic cytotoxic
activity. Thus, major differences exist between cord blood-derived and
BM-derived mononuclear cells with respect to their NK-cell-associated
cytotoxic behavior. This could have important implications for stem
cell transplantation phenomena, because it suggests that cord blood may
have increased potential for a GVL effect.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 207-213
© 1998 by The American Society of Hematology.
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