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 normal human donor peripheral blood were fractionated on columns charged with H. pomatia hemagglutinin (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 2 distinct fractions with 2 different concentrations of the competitive hapten N-acetyl-D-galactosamine (fraction II and III, respectively). Natural cytotoxicity of these lymphocytes to various tumor target cells (K562 [human myeloid leukemia], T24, MANO, HCV29 [human bladder transitional cell carcinoma lines]) was tested in a 51Cr release assay. Natural cytotoxicity was found in all 3 fractions recovered from the HP columns. In general, lymphocyte cytotoxicity in fractions I and II was significantly enhanced over that of unfractionated lymphocytes. Surface marker analysis and fractionation studies indicated that natural cytotoxicity in these target systems is exerted by HP+ and HP- lymphocytes bearing Fc receptors for Ig[immunoglobulin]G. Since the HP receptor is considered to be a T [thymus-derived] lymphocyte marker, a significant fraction of these NK [natural killer] 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 natural cytotoxicity of HP-column-fractionated lymphocytes to various degree, indicating that part but not all of it reflects antibody-dependent K-cell reactions. Since cytotoxicity in all 3 HP fractions was inhibitable in this way, Ig-dependent natural cytotoxicity may be displayed by HP+ and HP- effector cells.