Spontaneous cytotoxicity (SCMC) of normal human lymphocytes against a human melanoma cell line: a phenomenon due to a lymphotoxin-like mediator

J Immunol. 1976 Feb;116(2):342-8.

Abstract

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.

MeSH terms

  • Antibody Specificity
  • Cell Line
  • Cell-Free System
  • Cytotoxicity Tests, Immunologic
  • DNA / biosynthesis
  • Humans
  • Immunity, Cellular*
  • Lymphocytes / immunology*
  • Lymphotoxin-alpha / analysis
  • Lymphotoxin-alpha / pharmacology*
  • Melanoma / immunology*
  • Time Factors

Substances

  • Lymphotoxin-alpha
  • DNA