Suppression of activity of mouse natural killer (NK) cells by activated macrophages from mice treated with pyran copolymer

Abstract

Treatment of young mice with pyran copolymer caused a substantial decrease in natural killer (NK) cell activity at 7 days. The decrease in cytotoxicity was associated with the presence of splenic suppressor cells, capable of inhibiting in vitro the NK activity of spleen cells from normal mice. The suppressor cells appeared to be macrophages, being plastic-adherent, phagocytic and radioresistant, and lacking demonstrable Thy 1.2 antigen. Sonicates or culture supernatants of adherent spleen cells from pyran-treated mice were also able to inhibit NK activity, suggesting that suppressor cells act by release of soluble factors.

Development of hyporesponsiveness of natural killer cells to augmentation of activity after multiple treatments with biological response modifiers

“…However, our results failed to support either possibility: decreases in spleen cell numbers were not seen; rather there was a modest increase in the overall population, albeit not of a magnitude sufficient to account for the reduced NK activity. Using MVE-2 as a representative BRM to explore this phenomenon in more depth, we have examined the possible role of prostaglandin E [4,16] or the generation of cells capable of suppressing NK-effector function [24,25]. In a report to be published elsewhere (Saito T, Welker RD, Fukui H, Herberman RB, and Chirigos MA, Cellular Immunology, 1984, in press), we will present evidence against either of these potential mechanisms contributing to the development of hyporesponsiveness.…”

Basic and Interleukin-2-Augmented Natural Killer Cell Activity in Lichen planus

“…pyran copolymer. Corynebacterium parvum and other immune adjuvants [16], Theories concerning the origin and the nature of these sup pressor cells vary considerably. Santoni et al [16] suppose that a macrophage subset is responsible for the suppressor effect, while Tarkkanen et al [17] postulate that the sup pressor cells of NK activity are Fc-receptor-positive mature T lymphocytes.…”

Augmentation of Organ-Associated NK Activity by BRMs: Association of NK Activity with Mononuclear Cell Infiltration

“…This has been particularly perplexing in situations where the repeated administration of var ious BRMs, including IFN and pyran copo lymer, has resulted in depressed levels of NK activity [77,79,80]. One explanation for this effect would be the redistribution of NKactive cells from the NK-depressed sites (blood and spleen) to NK-augmented sites (lung and liver).…”

“…It has been dem onstrated that the single administration of some BRMs induced the development of suppressor cells which subsequently downregulated the NK activity in certain sites [54,71,[75][76][77][78][79]. These suppressor cells have been characterized in most cases as being adher ent, activated macrophages which can sup press the augmentation of NK activity in the spleen and/or blood of P. acnes [54,55,71,77] or pyran-treated mice [77,79]. It is not yet clear whether these suppressor cells de velop and suppress NK activity in other compartments.…”