title: Target cell-directed inactivation and IL-2-dependent reactivation of LAK cells.
abstract: In a previous study, we demonstrated that human natural killer cells (NK) lost their lytic activity after interaction with a sensitive target. The loss of NK activity also led to the loss of antibody-dependent cellular cytotoxicity (ADCC), prompting us to postulate that NK and ADCC activities may result from a common lytic mechanism. In this study, we examined whether nonadherent lymphocytes cultured 7 days in the presence of IL-2 (lymphokine-activated killer (LAK) cells) could also be inactivated and, subsequently, be reactivated in the presence of IL-2. We tested three populations of effector cells (EC): cells isolated from freshly drawn blood and tested immediately, cells cultured with IL-2 for 18 hr, and LAK cells. Once they have interacted with K562, all three cell populations lost greater than 90% of their NK-like lytic activity (NK-CMC) but only 80% of ADCC. However, when we treated the three cell types with antibody-coated K562, they lost 90-99% of NK-CMC and 90-97% of ADCC. In these inactivated effector cells we also observed: (i) a reduction in membrane expression of C-reactive protein; and (ii) a decrease in the expression of Leu-11a when EC were inactivated with antibody-coated K562. The loss of lytic activity against K562 was accompanied by a concomitant loss of activity against other LAK-sensitive targets as well as against antibody-coated targets (ADCC). In competitive inhibition experiments the inactivated effector cells failed to inhibit normal NK-CMC and ADCC activities mediated by fresh NK cells. As we have shown previously, this target-directed inactivation was not due to cell death or to lack of conjugate formation. Inactivated LAK cells regained their lytic potential when cultured with IL-2 and this effect was time dependent. By 72 hr, LAK cells inactivated with K562 regained 99% NK-CMC and 82% ADCC, whereas LAK cells inactivated with antibody-coated K562 regained only 80% NK-CMC and 70% ADCC. When we treated the effector cells with emetine, a potent inhibitor of protein synthesis, we could still inactivate the effector cells with K562 and with antibody-coated K562 but could not reactivate them with IL-2.
authors: Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.
authors: J
authors: J
authors: Xiao
authors: Z
authors: Z
authors: Brahmi
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004640:Emetine / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000494:pharmacology*
chemical_list: D007376:Interleukin-2; D008222:Lymphokines; D004640:Emetine