Level of activation determines whether inflammatory peritoneal and intratumoral macrophages will promote or suppress in vitro development of cytolytic T lymphocyte activity

Academic Article

Abstract

  • Mouse peritoneal macrophages that had been fully activated, i.e., made tumoricidal, in vitro either promoted or suppressed the in vitro development of cytolytic T lymphocyte activity, depending upon macrophage monolayer population density. Suppression was population density-dependent above 1,000 macrophages/mm2, whereas below this number, in vitro generation of killer T lymphocyte activity was enhanced substantially. These dual effects could not be attributed (a) to the differential survival of all lymphocytes or of just T lymphocytes or (b) to the participation of a non-T cytolytic effector cell type. In contrast, peritoneal macrophages that had been partially activated or primed (nontumoricidal but extremely sensitive to stimuli that trigger tumor cytotoxicity) in vitro were suppressive at all monolayer population densities tested. Furthermore, primed macrophages obtained from progressively growing murine sarcomas exerted a qualitatively similar density-dependent inhibition with no promotion of killer T lymphocyte activity at low population densities. These results define a second functional distinction between primed and activated macrophages in addition to their different tumoricidal capacities and suggest an explanation for the decline of T lymphocyte-mediated, antitumor responses frequently observed in hosts bearing progressively growing neoplasms.
  • Author List

  • Gillespie GY; Russell SW
  • Start Page

  • 535
  • End Page

  • 545
  • Volume

  • 27
  • Issue

  • 5