Immunoglobulin-Independent Natural Cytotoxicity of Fc Receptor-Bearing Human Blood Lymphocytes to Mumps Virus-Infected Target Cells

Abstract

The natural cytotoxicity of peripheral blood lymphocytes (PBL) from healthy human donors to mumps virusinfected target cells was studied by a ⁵¹Cr-release assay. Neuraminidase-treated PBL were fractionated on columns charged with Helix pomatia A-hemagglutinin (HP) coupled to Sepharose. Cytotoxicity was found both in the fraction depleted of lymphocytes with HP receptors (HP⁺) but enriched in B and null cells and in two fractions containing HP⁺ cells, mainly considered to be T cells. The cytotoxic activity of the three fractions was well correlated with their content of lymphocytes with Fc receptors for IgG (FcR⁺). That FcR⁺ lymphocytes were indeed the effector cells in this system was further shown by fractionating the lymphocytes through columns charged with immune complexes (ovalbumin/rabbit anti-ovalbumin). Those columns that depleted the passed cell preparation of FcR⁺ cells also efficiently reduced cytotoxicity to the virus-infected target cells. In contrast, columns that were charged with F(ab′)₂ fragments of rabbit anti-immunoglobulin and that completely removed sIg⁺ B cells did not significantly affect cytotoxicity. Taken together, the results indicate that the effector cells in this system are FcR⁺ sIg^- cells and that a significant fraction of them appear to be T cells. However, some effector cells may lack T cell markers and may be null cells. This surface marker profile is very similar to that of antibody-dependent K cells as well as to that of lymphocytes displaying natural cytotoxicity to uninfected target cells (NK). We have previously shown that human NK cytotoxicity to uninfected target cells is frequently immunoglobulin dependent since it is strongly inhibited by addition of Fab fragments of purified rabbit antibodies to human immunoglobulin. Using this procedure we found that the natural cytotoxicity against the virus-infected target cells was not inhibited by Fab anti-immunoglobulin. In contrast, the strongly enhanced cytotoxicity obtained by inclusion in the experiment of a human anti-mumps serum was abolished. These results indicate that the eleyated natural cytotoxicity to mumps virus-infected target cells by lymphocytes from healthy donors is antibody independent, reflecting a virus-dependent but immunologically nonspecific activation of effector cells.