TNF-alpha further augments natural killer cells when co-administered with an interferon inducer to irradiated, leukemic, bone-marrow-transplanted mice.
OBJECTIVE
We have recently demonstrated that the interferon inducer Poly I:C significantly augments both natural killer (NK) cell numbers and the life span of leukemic, irradiated mice given syngeneic bone marrow transplants (SBMT). The cytokine tumor necrosis factor-alpha (TNF-alpha) also stimulates NK cells directly through receptor-ligand mechanisms. We have combined in the present study the NK-enhancing properties of IFN (Poly I:C-induced) and TNF-alpha by giving Poly I:C to leukemic mice for 8 days after irradiation and SBMT, concomitant with TNF-alpha during the first 4 days immediately after SBMT. All mice were sampled at day 9 following irradiation, transplant, and treatment.


METHODS
NK cells were identified and quantified by immunoperosidase labeling methods combined with a hematologic staining technique.


RESULTS
The data reveal that TNF-alpha, added to the Poly I:C administration protocol, significantly boosted NK cell numbers 2.4-fold over that achieved by Poly I:C alone.


CONCLUSIONS
Since the role of NK cells in the immediate post-transplant period is (a) to destroy residual tumor cells, and (b) to produce hemopoiesis-driving cytokines, it appears that two NK cell stimulants are better than one, at least in the crucial, early post-transplant period.
Department of Anatomy & Cell Biology, McGill University, Montreal, QC, Canada.
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Currier
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Miller
D000818:Animals; D016026:Bone Marrow Transplantation; D007369:Interferon Inducers / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007942:Leukemia, Experimental / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D007369:Interferon Inducers; D014409:Tumor Necrosis Factor-alpha; D011070:Poly I-C