High release of tumor necrosis factor alpha, interferon gamma and interleukin-6 by adherent lymphokine-activated killer cells phenotypically derived from T cells

Abstract

Adherent lymphokine-activated killer cells (A-LAK) are highly potent cytotoxic cells, which are shown to be derived not only from natural killer (NK)/K cells but phenotypically also from T cells. The generation and phenotypical and functional characterisation of these T-cell-derived A-LAK are described. In contrast to non-adherent cells (NA-LAK) and unseparated LAK (UN-LAK), these mostly CD3+ CD56+ CD8+ cells display a high degree of expansion following initial interleukin-2 (rIL-2) activation and further culturing in autologous conditioned medium. A comparison of cytotoxic activities of cultured cells reveals a significantly higher oncolytic ability of A-LAK cells against both K562 and Daudi cells than that of cultured controls of NA-LAK and UN-LAK. In addition, A-LAK are characterised by a marked endogenous cytokine release of interferon gamma, tumour necrosis factor alpha and IL-6 as well as by their shedding of p55 IL-2 receptor after exposure to IL-2. The results demonstrate A-LAK to be the lymphocyte subpopulation with the most cytotoxic activity and endogenous cytokine release after exposure to IL-2. The improvement of techniques for long-term cultures may be of interest for future therapeutic approaches.