Heterogeneity amongst natural killer cells revealed by limiting dilution culture; selectivity against virus-infected and tumour cell targets.

Previous studies have suggested that natural killer (NK) cells exhibit heterogeneous cytotoxicity towards different tumour cell targets. No studies have set out to determine whether different NK populations have relative selectivity for virus-infected cells. The aims of this study were to determine if this was the case for short-term clones, and whether there were differences in relative selectivity for particular target cells between clones with NK activity but with different surface phenotypes. Cells from different starting populations [whole peripheral blood lymphocytes (PBL), E-rosette positive or negative, CD16+ or CD3- cells] were grown in limiting dilution culture (LDC) with interleukin-2 (IL-2). The precursor frequency (NK-p) of cells proliferating and exhibiting NK activity towards various virus-infected or uninfected fibroblasts or tumour cell targets was determined by split-well analysis of the LDC. The relative NK-p were similar for different individuals, but were much lower for virus-infected fibroblasts than a tumour cell target. The pattern of cytotoxicity of 757 short-term clones, identified from the LDC, against four to five tumour and virus-infected target cells were analysed. We conclude that there was selective lysis of virus-infected cells by a proportion of NK clones which were predominantly PBL-derived (mainly CD3+). Twenty-six per cent of E(+)-derived clones lysed Molt4 cells only in the absence of phytohaemagglutinin (PHA), and a proportion of PBL- or E(+)-derived clones (up to 44%) lysed uninfected or virus-infected fibroblasts but not Molt4+PHA. Thus, under hese conditions lectin-induced cytotoxicity does not detect total potential cytotoxicity.