ROLE OF ENHANCED CELLULAR ADHESION IN IL-6-AUGMENTED LYMPHOKINE-ACTIVATED KILLER-CELL FUNCTION

The authors demonstrated previously that a short-term treatment with I L-6 of lymphokine-activated killer (LAK) cells produces an increase in cytotoxic activity of CD56(+)/CD3(-) effector cells generated from hu man PBL as well as from human thymocytes. In the study described here, the mechanisms by which IL-6 enhances LAK cytotoxicity were examined. Like untreated LAK cells, IL-6-treated LAK cells require Ca++ to init iate cytolysis. However, IL-6 treatment of LAK cells does not alter th e rate of programming for lysis. Instead, IL-6 increases target-bindin g capacity of CD56(+)/CD3(-) LAK cells in association with the increas ed cytotoxicity. Similar to target-binding of untreated LAK cells, the binding between IL-6-treated LAK cells and target cells is dependent on Mg++. Cellular adhesion molecules (CAM), CD11a-c, CD18, CD54, CD56, CD58 and CD2 (T11(1) epitope), are up-regulated in LAK cells by cultu re with IL-2. Among MoAbs to these CAMs, only Abs to CD11a/CD18 (LFA-1 ) and CD54 (ICAM-1) decrease both target-binding and cytolysis by LAK cells. IL-6 treatment changes neither the proportion nor the intensity of CAM positive cells. However, MoAbs to CD11a/CD18 and CD54 reduce b oth target-conjugation and cytotoxicity of IL-6-enhanced LAK cells to the same level as control LAK cells treated with the MoAbs. IL-6-enhan ced LAK functions (both target-conjugation and target-lysis) are not a brogated by MoAbs to other CAM which do not inhibit standard LAK funct ions. These results indicate that IL-6 up-regulates cellular events me diated by CD 11a/CDI8 and CD54 molecules which are involved in standar d LAK functions. These events may result in activation of lytic effect or cells, associated with an increase in target-binding and an increas e in cytotoxicity.