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.