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Generation of human natural killer cells from immature progenitors does not
require marrow stromal cells
MR Silva, R Hoffman, EF Srour and JL Ascensao
University of Nevada School of Medicine, Reno.
Human natural killer (NK) cells comprise 10% to 15% of peripheral blood
mononuclear cells and have an important role in immune responses against
tumors, viral infections, and graft rejection. NK cells originate in bone
marrow (BM), but their progenitors and lineage development have not been
completely characterized. We studied the generation of NK cells from
purified CD34+HLADR- and CD34+HLADR+ BM progenitors and the influence of
various cytokines on their production. We show that CD3-CD56+ cytotoxic NK
cells can develop from both progenitors populations when interleukin-2
(IL-2) is present in an in vitro suspension culture system containing IL-1
alpha and stem cell factor. Up to 83.8% and 98.6% CD3-CD56+ cells were
detected in CD34+HLADR- and CD34+DR+ cultures, respectively, after 5 weeks
of culture; significant numbers of NK cells were first detected after 2
weeks. Cytotoxic activity paralleled NK cell numbers; up to 70% specific
lysis at an effector:target ratio of 10:1 was observed at 5 weeks. IL-7
also triggered development of CD3-CD56+ cells from these immature
progenitors (up to 24% and 55% appeared in CD34+HLADR- and CD34+HLADR+
cultures, respectively). Our data suggest that BM stromas are not necessary
for NK cell development and that IL-2 remains essential for this lineage
development and differentiation.
Volume 84,
Issue 3,
pp. 841-846,
08/01/1994
Copyright © 1994 by The American Society of Hematology
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