Cytokine-induced enhancement of the susceptibility of hairy cell leukaemia lymphocytes to natural killer cell lysis.

In seven patients with HCL we have investigated how the cytokines TNF, alpha and gamma IFN and IL2 modify the interactions between HCL lymphocytes and MHC unrestricted cytotoxic effector cells [natural killer (NK) and lymphokine activated killer (LAK), cells]. We find that IL2 and alpha IFN increase patient NK activity against K562, though killing remains subnormal. IL2 and alpha IFN also induce normal levels of LAK activity, measured against an NK resistant B lymphoblastoid cell line. In contrast, gamma IFN has no effect on patient effector function. However, promotion of cytotoxic effector activity is unlikely to produce therapeutic benefit since HCL cells themselves are entirely resistant to NK/LAK killing. Susceptibility of HCL cells can be induced by culturing the cells in the presence of both gamma IFN and TNF, but not by culture with either cytokine alone. This synergy is not mediated by a gamma IFN induced increase in TNF receptors on HCL lymphocytes, and therefore occurs at a post-receptor level.