High release of tumor necrosis factor alpha, interferon gamma and interleukin-6 by adherent lymphokine-activated killer cells phenotypically derived from T cells.
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.
Koberda
J
J
Department of Internal Medicine, J. W. Goethe University, Frankfurt/M., Federal Republic of Germany.
Bergmann
L
L
Mitrou
P S
PS
Hoelzer
D
D
D002448:Cell Adhesion; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma