[Involvement of tumor necrosis factor in the generation of LAK killer cells].

The effect of Tumor Necrosis Factor (TNF) alpha on LAK generation was investigated. TNF was found to act synergistically with low concentrations of IL-2 (15 pM), which were ineffective by themselves to promote the differentiation of Large granular lymphocytes (LGL) into LAK effectors. The IL-2/TNF driven generation of LAK activity involves the induction of high affinity IL-2 receptors on LGL and occurs without promoting a significant proliferation, suggesting a functional activation rather than a proliferative expansion of LAK precursors. Our studies also indicate the existence of a correlation between the generation of LAK activity and the increase in TNF binding sites on LGL. Furthermore we demonstrate that the failure of low doses of IL-2 to induce LAK activity were related to their incapacity to induce TNF production by LGL and suggest that TNF alpha may be a physiologic mediator in the sequential activation stages of LGL into LAK effectors.