Specificity of Natural Cytotoxic Reactivity of Normal Human Lymphocytes Against a Myeloid Leukemia Cell Line

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Abstract
Natural reactivity of normal human peripheral blood lymphocytes against cultured cells derived from tumors was demonstrated by various cytotoxic assays. We used a 4-hour, cytotoxic inhibition assay to examine the specificity of reactivity of this natural killing. K-562, a suspension myeloid cell line derived from the pleural effusion of a patient with chronic myelogenous leukemia, was used as the target cell in all assays. Fresh and frozen human lymphocytes were tested as attacker cells. Competitive inhibition of the reactivity was performed by the addition of varying numbers of unlabeled (inhibitor) cells to a standard mixture of lymphocytes and labeled target cells (100:1). The inhibition studies demonstrated a broad but reproducible pattern of specificity, with most but not all established human cell lines tested being significantly inhibitory of the cytotoxic reaction. Fresh single cell suspensions from malignant tissues and cell lines derived from carcinomas of the breast and lung and from acute myelogenous and lymphoblastic leukemias gave positive results. However, some established human cell lines (grown under the same conditions as the positive lines), cryopreserved leukemia blast cells obtained directly from patients, and normal peripheral blood lymphocytes caused either no inhibition or nonspecific inhibition of reactivity. Positive results were not limited to human cells: Mouse and rat lymphoma cells passaged in vivo or in culture, but neither normal murine Iymphoid cells nor mouse fetal tissue could inhibit the cytotoxicity against K-562. These studies indicated that the cytotoxicity of normal human peripheral blood lymphocytes against K-562 is specific and is directed against antigen(s) present on many human established cell lines and on some human and murine tumors.