Spontaneous cytotoxicity (SCMC) of normal human lymphocytes against a human melanoma cell line: a phenomenon due to a lymphotoxin-like mediator.
Spontaneous cell-mediated cytotoxicity (SCMC) of normal human lymphocytes against various allogenic tumor cell lines has recently been identified as a non-T lymphocyte function. In this study evidence is presented that SCMC against a human melanoma cell line (IGR3) involves a nonspecific lymphotoxin-like mediator(s) (LT), which is rapidly produced by lymphocytes that are retained on IgG-anti-IgG columns. LT was shown to inhibit in 48-hr cultures the DNA synthesis of growing IGR3 and HeLa cell monolayers. Furthermore, in short term 51Cr-release assays using IGR3 target cells, LT increased strongly the SCMC of normal allogeneic lymphocytes, although it exhibited little cytotoxicity by itself in this assay. LT was detectable in cell-free supernatants harvested after 6 hr from co-cultures of IGR3 melanoma cells and normal effector lymphocytes, but not in supernatants from melanoma cells alone or lymphocytes alone. Lymphocyte preparations that had been passed through IgG-anti-IgG columns had lost the capacity to generate LT and were poor effectors in SCMC. However, in the presence of LT, a small proportion of null cells, which pass through IgG-anti-IgG columns, was capable of inducing strong SCMC. Absorption of the supernatants, containing LT activity, with an insolubilized rabbit-anti-human IgG antiserum did not remove the mediator, suggesting that it is not an immunoglobulin.
D000918:Antibody Specificity; D002460:Cell Line; D002474:Cell-Free System; D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007111:Immunity, Cellular; D008214:Lymphocytes / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000032:analysis / Q000494:pharmacology*; D008545:Melanoma / Q000276:immunology*; D013997:Time Factors
D008233:Lymphotoxin-alpha; D004247:DNA