Spontaneous Cell-Mediated Cytotoxicity in Humans: Role of Interferon and Immunoglobulins

Abstract

Abstract Human lymphocytes secrete high levels of interferon a few hours after being cultured with certain tumorderived or virus-transformed cell lines. Interferon and interferon inducers (e.g., viruses, inducer cell lines, synthetic inducers), after short incubation with lymphocytes, increase several-fold the cytotoxicity of human natural killer cells. When lymphocytes are tested as effector cells against interferon-inducing target cell lines in an 18-hr test of spontaneous cell-mediated cytotoxicity, the enhancing effect of the interferon released in the culture medium is responsible for 80 to 90% of the total cytotoxicity observed. The ability or inability of different target cell lines to induce interferon is responsible for the apparent difference in selectivity of the cytotoxicity against various targets when fresh lymphocytes, cultured lymphcoytes, or interferon-activated lymphocytes are used as effector cells. Moreover, some of the apparently specific results obtained in competitive assays with unlabeled target cells are also dependent on the ability or inability of the competitor and target cells to induce interferon. Interferon does not increase the antibody-dependent cytotoxicity mediated by human lymphocytes, which suggests that spontaneous and antibody-dependent cell-mediated cytotoxicity are mediated by different effector cells or that a unique class of effector cells can mediate cytotoxicity with two independent mechanisms. The inability of rabbit F(ab′)2 fragment antihuman IgG to inhibit spontaneous cell-mediated cytotoxicity, renders unlikely the possibility that the activity of the human natural killer cells is dependent on cytophilic anti-target cell antibodies adsorbed in vivo to the effector lymphocytes.