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Anti-asialo GM1 antiserum treatment of lethally irradiated recipients
before bone marrow transplantation: evidence that recipient natural killer
depletion enhances survival, engraftment, and hematopoietic recovery
P Tiberghien, DL Longo, JW Wine, WG Alvord and CW Reynolds
Biological Carcinogenesis Development Program, Program Resources, Inc.,
Frederick, MD.
Natural killer (NK) cells are reported to have an important role in the
resistance of lethally irradiated recipients to bone marrow transplantation
(BMT). Therefore, we investigated the effects of recipient NK depletion on
survival, chimerism, and hematopoietic reconstitution after lethal
irradiation and the transplantation of limiting amounts of T-cell-deficient
bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1)
antiserum treatment, effective in depleting in vivo NK activity, was
associated with a marked increase in survival in 3 of 3 allogeneic
combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced
survival was independent of the susceptibility of each recipient strain to
accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also
effective in increasing survival in recipients of syngeneic BM, suggesting
that NK cells can adversely affect engraftment independent of genetically
controlled polymorphic cell surface determinants. Analysis of chimerism in
surviving animals 2 months post-BMT showed that recipient NK depletion
significantly increased the level of donor engraftment when high doses of
BM were transplanted. These studies also demonstrated that anti-ASGM1
pretreatment mainly resulted in an increase in extramedullary hematopoiesis
in the second and third week after irradiation. Anti-ASGM1 treatment also
dramatically accelerated the rate of appearance of donor-derived cells with
a higher level of donor- cell engraftment apparent at a time when the
differences in survival between NK-depleted and control BMT recipients
became significant. Peripheral cell counts were also affected by NK
depletion, with significantly enhanced platelet and red blood cell recovery
and a moderate increase in granulocyte recovery. The overall favorable
influence of anti-ASGM1 recipient treatment on hematopoietic events
post-BMT suggests that, in humans, pretransplant regimens aimed toward NK
depletion should be evaluated.
Volume 76,
Issue 7,
pp. 1419-1430,
10/01/1990
Copyright © 1990 by The American Society of Hematology

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