Heterogeneity and mechanism of action of human natural killer lymphocytes: differential distribution of receptors for Helix pomatia haemagglutinin (HP receptors)

Abstract

Neuraminidase-treated lymphocytes from the peripheral blood of normal human donors were fractionated on columns charged with Helix pomatia haemagglutinin (HP) coupled to Sepharose 4B. While lymphocytes lacking HP receptors (HP-) passed directly through the column (fraction I), lymphocytes with HP receptors (HP+) were subsequently eluted in two distinct fractions with two different concentrations of the competitive hapten N-acetyl-D-galactosamine (fraction II and III, respectively). The natural cytotoxicity of these lymphocytes to various tumour target cells (K562, T24, MANO, HCV29) was tested in a 51Cr release assay. Natural cytotoxicity was found in all three fractions recovered from the HP columns. In general, the cytotoxicity of the lymphocytes in fractions I and II was significantly enhanced over that of the unfractionated lymphocytes. Surface marker analysis and fractionation studies indicated that natural cytotoxicity in these target systems is exerted by both HP+ and HP- lymphocytes bearing Fc receptors for IgG. Since the HP receptor is considered to be a marker to T lymphocytes, the findings suggest that a significant fraction of these NK cells may be of T-cell lineage. The surface marker profiles of these NK cells are very similar to those of antibody-dependent K cells. Addition of Fab fragments of immunoadsorbent-purified rabbit antibodies to human immunoglobulin inhibited the natural cytotoxicity of HP-column-fractionated lymphocytes to various degrees, indicating that part but not all of it reflects antibody-dependent K-cell reactions. Since cytotoxicity in all three HP fractions was inhibitable in this way, the results suggest that immunoglobulin-dependent natural cytotoxicity may be displayed by both HP+ and HP- effector cells.