Immunology Letters, 41 (1994) 13-17 0165 - 2478 / 94 / $ 7.00 © 1994 Elsevier Science B.V. All rights reserved IMLET 02116 Discrepancy between direct and antibody-dependent cytotoxic activities of human LAK cells Michael P. Potapnev a'*, Tatyana S. Garbuzenco a, Natalia V. Goncharova a, Vladimir D. Zobnin a, Oleg V. Shadrin b and Svetlana N. Bykovskaya b ~Institute of Hematology and Blood Transfusion, Minsk 223059, Belarus; bCancer Research Centre, Moscow 115478, Russia (Received 20 January 1994; accepted 16 February 1994) 1. Summary Human lymphokine-activated killer (LAK) cells display cytotoxic activity against natural killer (NK)-resistant tumor cells in an antibody-indepen- dent and -dependent manner. We compared LAK cell-mediated antibody-independent cytotoxicity (LAK activity) and antibody-dependent cellular cyto- toxicity (ADCC) against untreated and antibody- coated Raji cells, respectively. Human lymphocytes showed drastically increased LAK activity after sti- mulation with interleukin-2 (IL-2) for 3 or 7 days when compared to non-activated cells. The level of ADCC was reduced for 3-day-generated LAK cells and augmented for 7-day-generated LAK cells as compared to non-activated cultured lymphocytes. Phenotypical analysis revealed IL-2-induced up-regu- lation of the proportion of CDIIb + (but not CD16 +) lymphocyte subpopulation in 7-day-gener- ated LAK cells. The data imply that human LAK cells exhibit antibody-dependent and -independent cytotoxic activities via distinct effector pathways at different stages of generation. These stages may be associated with changes in adhesion molecule (CD 1l b/CD 18) expression on the surface of IL-2-ac- tivated lymphocytes. 2. Introduction Lymphokine-activated killer (LAK) cells have Key words: Lymphokine-activated killer cell; Phenotyping; Direct cytotoxicity; Antibody-dependent cellular cytotoxicity; (Human) *Corresponding author: Michael P.Potapnev, Institute of Hematol- ogy and Blood Transfusion, Dolginovsky tr. 160, 223059, Minsk, Belarus. been shown to exert strong anti-tumor activity in vivo and in vitro [1,2]. Generation of LAK cells in culture of human peripheral blood lymphocytes acti- vated with interleukin 2 (IL-2) for short (2-3 days) or long (7-10 days) term may induce accordingly natur- al killer (NK)-like or T-cell-like LAK cells as esti- mated on the basis of phenotypical marker differ- ences [3,4]. Nevertheless, direct cytotoxic activity of LAK cells has been shown not to depend upon their NK/T-cell-related surface markers [5]. LAK cells also exert indirect, antibody-dependent cellular cytotoxi- city (ADCC) after induction with IL-2 in vivo and in vitro [6]. It is known that both resting and acti- vated lymphocytes display ADCC and that FcTR- bearing NK-like cells are the principal effector lym- phocytes [7,8]. We have undertaken a comparative study of the direct cytotoxic (LAK) and indirect (ADCC) activ- ities of short- and long-term generated LAK cells. We found that after IL-2 activation for 3 days or 7 days human lymphocytes exhibit a different profile of LAK and ADCC activities and peculiarities in CD16 and CD1 lb/CD18 surface molecules expression may be associated with these differences. 3. Materials and Methods 3.1. Cells Mononuclear cells were isolated from fresh hepar- inized donor blood by a standard Ficoll/Hypaque centrifugation procedure. Purified lymphocytes were obtained from mononuclear cells treated with carbo- nyl iron (4.5-5.2 /tm, Sigma) to delete phagocytic cells (monocytes). Immunofluorescent analysis of purified lymphocytes indicated < 0.1% contamina- SSDI 0165-2478(94)00032-M