Regulation of activation and proliferation of human natural killer cells.

Abstract

Human peripheral blood lymphocytes from all healthy donors are able to lyse in vitro a variety of target cells, including normal, tumor-derived and virus-infected cells, in the absence of previous sensitization against target cell antigens (1). Although lymphocytes from different donors show a large variability in their cytotoxic ability, the rank of cytotoxicity against different target cell lines depends on the susceptibility of the cell lines to the cytotoxic cells and not on the individual variations among lymphocyte donors. Unlike specific cytotoxicity mediated by cytotoxic T cells, this natural cytotoxicity is not restricted by antigens of the major histocompatibility complex (HMC). The human target cell line most used as a target, the myeloerythro leukemic K562 line, expresses neither class I nor class II MHC antigens. The effector cells responsible for this spontaneous cytotoxicity have been defined natural killer (NK) cells and morphologically identified as large granular lymphocytes (LGL). LGL are light density medium- to large-sized lymphocytes characterized by abundant cytoplasm, indented nucleus and few distinct azurophilic granules (2). Separation of lymphocytes on Percoli gradients has been extensively used to obtain enriched preparations of LGL (3). Although this technique was instrumental for much of our advanced knowledge of NK cell biology. LGL preparations obtained with Percoli gradients are not pure NK cells and the contaminant cell types, even if present in a low proportion, have often been responsible for artifactual results and erroneous attributions of functions to NK cells.