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Hematopoietic stem cells are not direct cytotoxic targets of natural killer
cells
HL Aguila and IL Weissman
Department of Pathology Stanford University School of Medicine, CA. 94305,
USA.
Bone marrow (BM) transplants from one individual to an irradiated
histoincompatible individual of the same species are rejected. In mice, the
primary host barrier cells that recognize bone marrow grafts bearing
hematopoietic histocompatibility antigens bear surface markers of natural
killer (NK) lymphocytes. Because of the innate ability of NK cells to kill
susceptible targets, it has been proposed that the cytotoxic bone marrow
graft rejection. To test this hypothesis, we purified hematopoietic stem
cells from mice and incubated them with purified populations of actively
cytotoxic allogeneic and semisyngeneic NK cells, followed by analysis of
the ability of the treated hematopoietic stem cells (HSCs) to rescue
lethally irradiated syngeneic animals. Such rescue was unimpaired. Also,
HSC allografts were transplanted into transgenic mice deficient in NK and
killer T-cell cytotoxicity generated by expressing diphtheria toxin A chain
under the control of granzyme A promoter. Allogeneic HSCs were susceptible
to allogeneic restriction in these mice, implying that the effector
functions of NK marker-positive cells do not require NK cell cytotoxicity.
Volume 87,
Issue 4,
pp. 1225-1231,
02/15/1996
Copyright © 1996 by The American Society of Hematology
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