Kinetic Analysis of the Inhibition of Natural Killer (NK) Activity by Multiple Populations of Tumor-Activated Suppressor Cells

Abstract

Previous studies have shown that the progressive growth of the M-1 fibrosarcoma in DBA/ 2J mice is associated with the activation of suppressor cells which inhibit both mitogeninduced proliferative responses and antibody synthesis. In this study, we have analyzed the effect of tumor growth on NK cell activity. Mice in the advanced stages of tumor growth did have a significant depression in NK activity, and this depression could not be overcome by the injection of the interferon inducer, polyinosinic-polycytidylic acid (Poly I:C). The decline in NK activity was associated with the presence in the spleens of suppressor cells capable of inhibiting the NK activity of spleen cells from Poly I:C-treated syngeneic mice. In order to characterize the suppressor cells, we used a combination of negative selection procedures and kinetic analysis. These studies demonstrated that the spleens of tumor-bearing mice contained two distinct populations of suppressor cells which were not evident in normal mice. One population was non-adherent to nylon wool, Thy-1 -, non-phagocytic, did not bind target cells, and had a non-competitive mechanism of suppression. The second population was adherent, Thy-1 -, phagocytic, and had a competitive mechanism of suppression. In addition, the spleens of both normal and tumor-bearing mice contained an adherent, non-competitive suppressor cell population which was enriched following negative selection procedures removing T cells or phagocytic cells.