TNF-α further augments natural killer cells when co-administered with an interferon inducer to irradiated, leukemic, bone-marrow-transplanted mice

Abstract.

Purpose: 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-α (TNF-α) 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-α by giving Poly I:C to leukemic mice for 8 days after irradiation and SBMT, concomitant with TNF-α 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-α, 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.