Differential effects of various cytokines on the generation of rat LAK cells from their purified precursors.

The regulation of rat lymphokine-activated killer (LAK) cell generation from their purified precursors using various cytokines was studied. Several important findings emerged from this study. These include: (i) interleukin-2 (IL-2), but not any other cytokine tested, is pivotal for the development of LAK cells; (ii) transforming growth factor beta 1 (TGF-beta) inhibits IL-2-induced LAK cell differentiation, but not proliferation, regardless of the dose of IL-2 used; (iii) interferon-gamma (IFN-alpha) is inhibitory for LAK cell proliferation, but not differentiation; (iv) tumour necrosis factor-alpha (TNF-alpha) or IFN-gamma synergize with a low but not a high concentration of IL-2; (v) TNF-alpha reverses the anti-differentiative activity of TGF-beta 1 in the presence of a high, but not a low, concentration of IL-2; (vi) anti-p55 IL-2 receptor (R) is not inhibitory for LAK cell development but, on the contrary, a low concentration of this antibody synergizes with IL-2; (vii) IL-1 alpha, IL-1 beta, IL-3, IL-4, IL-6, IFN-alpha. TNF-alpha, or TGF-beta 1 do not affect LAK cell function; and (viii) IL-2 may provide two separate signals for LAK precursors: one is proliferative and the other is differentiative.