Concomitant effect of 2'-deoxycoformycin on natural killer cell activity and tumour cell sensitivity to lysis in hairy cell leukaemia--discordant effects of alpha interferon.
The effects of 2'-deoxycoformycin (dCF) and alpha interferon (IFN-alpha) on natural killer (NK) cell-enriched fractions and hairy cell (HC) targets from three patients with HC leukaemia (HCL) were investigated. There was no significant increase in NK activity when either the HC targets or NK-enriched cells were preincubated with dCF. However, preincubation of both HC and NK cells with dCF resulted in increased NK activity. Culture of enriched NK cells with IFN-alpha enhanced their activity. However, preincubation of HC targets with this drug in the presence or absence of dCF resulted in a protective effect. Maximal NK activity towards HCL was obtained when the target tumour cells were separately precultured with dCF and the NK-enriched effectors precultured with dCF + IFN-alpha. The effect of dCF and IFN-alpha was also measured using the standard K562 cells as targets for NK activity. dCF enhanced NK activity following preculture of both effector and target K562 cells, but IFN-alpha did not reduce K562 cell susceptibility to NK lysis as it did for HC cells. Our findings suggest that (a) dCF and IFN-alpha, which are used to treat HC, could function via activation of NK cells, (b) effects on both effector and tumour target cells should be taken into account, and (c) caution should be exercised in extrapolating the effects of NK-cell activity against K562 cells to those on HC targets.
Lahat
N
N
Immunology Unit, Lady Davis Carmel Hospital, Haifa, Israel.
Aghai
E
E
Merchav
S
S
Kinarty
A
A
Sobel
E
E
Froom
P
P
D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007943:Leukemia, Hairy Cell / Q000188:drug therapy / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D015649:Pentostatin / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D015649:Pentostatin