Its Role in Cytotoxic Effec tor Funct

Recent studies in both human and murine systems have suggested that natural killer (NK) t activity can be mediated by different populations of effector cells (1-3). In human peripheral blood, most NK cells were found in the null cell fraction (4) and were morphologically identified as large granular lymphocytes (LGL) (5). When analyzed with monoclonal antibodies directed at well-defined surface structures, purified LGL were shown to be a heterogeneous population of cells, probably containing various subsets. For example, 30% of LGL react with anti-T8, 70-80% with anti-T11 and/or anti-Mol, and 40-50% with antiT 10 (6-8). In addition, many studies have demonstrated that not only LGL but also activated T lymphocytes were able to mediate NK or NK-like activity (911). To both dissect the heterogeneity of NK cells and subsequently perform studies with homogeneous populations of these cytotoxic lymphocytes, we have recently developed human NK clones (7). This approach was made possible by previous studies which demonstrated that NK cells can be cultured and expanded in conditioned medium containing interleukin 2 (IL-2), and that cultured cells maintain stable phenotype and functional activity for prolonged periods of time in vitro (12, 13). Furthermore, when a series of human NK clones was analyzed with monoclonal antibodies, their phenotypic heterogeneity confirmed previous observations made with uncloned populations of cells (14). Three groups of clones could be distinguished by analysis of cell surface markers. One group was