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Activated natural killer cells and interleukin-2 promote granulocytic and
megakaryocytic reconstitution after syngeneic bone marrow transplantation
in mice
AK Siefer, DL Longo, CL Harrison, CW Reynolds and WJ Murphy
Laboratory of Leukocyte Biology, Program Resources, Inc/DynCorp, National
Cancer Institute-Frederick Cancer Research and Development Center
(NCI-FCRDC), MD 21702-1201.
Purified populations of natural killer (NK) cells were obtained from mice
with severe combined immune deficiency (SCID). SCID spleen cells were
cultured and activated with recombinant human interleukin-2 (rhIL- 2) in
vitro. The activated NK cells were then transferred with syngeneic BALB/c
bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic
recipients to determine their effect on long-term hematopoietic
reconstitution. On analysis, the transfer of rhIL-2- activated NK cells
along with BMC resulted in significant increases in splenic and BM
hematopoietic progenitor cells when compared with those for mice not
receiving NK cells. Histologic and flow cytometric analysis showed a marked
increase in granulocytic and megakaryocytic lineage cells present in the
spleens of the mice receiving activated NK cells. Analysis of the
peripheral blood indicated that the transfer of activated NK cells with BMC
also significantly improved platelet and total white blood cell counts,
with increases in segmented neutrophils. Erythroid recovery was not
affected. Finally, lethally irradiated mice receiving activated NK cells
and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked
increase in survival rate. These results show that the use of populations
enriched for activated NK cells after syngeneic BM transplantation (BMT)
has a profound enhancing effect on engraftment primarily affecting
megakaryocytic and granulocytic cell reconstitution. Therefore, the
transfer of activated NK cells and rhIL- 2 may be of clinical use to
promote hematopoietic reconstitution after BMT.
Volume 82,
Issue 8,
pp. 2577-2584,
10/15/1993
Copyright © 1993 by The American Society of Hematology
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