Lymphokine-activated effector cells: modulation of activity by cytokines

Interleukin 2 (IL-2) has been demonstrated to generate lymphokine-activated killer (LAK) cells from normal human peripheral blood lymphocytes (PBL). Such LAK cells have demonstrated lytic activities on certain tumor cell targets including melanoma, renal carcinoma, and other tumor targets. B lymphoblastoid cell lines such as Raji cells are routinely employed to assess functional LAK cell activity. In our studies we have assessed the effect of various cytokines that affect lymphocyte cell growth and differentiation, including rIL-2, interleukin 4 (rIL-4), interleukin 6 (rIL-6), interferon alpha and gamma (rIFN-alpha and -gamma) and tumor necrosis factors alpha and beta (rTNF-alpha, rTNF-beta), for their ability to generate functional LAK cell activity. Our data confirm that rIFN-alpha and -gamma singularly are capable of inducing LAK cell activity (55 +/- 21 and 40 +/- 10, respectively, in comparison to rIL-2 at 1000 units/ml) whereas rIL-4, rIL-6, BCGF, rTNF-alpha, or rTNF-beta failed to generate the functional LAK cell activity from human PBL. Interferon alpha, itself capable of generating LAK cell activity, was augmentative in its effect with rIL-2 for the generation of functional LAK cell activity. Conversely, rIL-4 inhibited LAK cell activity induced by either rIL-2 alone or the combination of rIL-2 and rIFN-alpha. Furthermore, the increased effects of rIFN-alpha with rIL-2 on LAK cell activity are partly abrogated by as much as 30 or 52% by delaying the addition of either rIL-2 or rIFN-alpha, respectively, for more than 24 h. These results suggest a regulatory role for certain cytokines on LAK cell functions.