Regulation of lymphocyte activation: macrophage-dependent suppression of T lymphocyte protein synthesis.

We investigated the influence of macrophages on lymphocyte protein synthesis in C57Bl/6N mice. When activated macrophages recovered from MSV-induced regressing tumors or peritoneal macrophages induced by C. parvum injection were cultured for 6 hr with resting or Concanavalin A-stimulated normal spleen cells, a decrease of protein synthesis was observed. In contrast, peritoneal macrophages induced by injection of light mineral oil or a macrophage cell line, WEHI-3, were completely ineffective. When the mixed cultures of normal spleen cells and macrophages were fractionated, we found that Thy 1.2-positive, nylon-nonadherent cells, but not plastic adherent cells, had a depressed protein synthesis. The suppressor cells, on the contrary, were Thy 1.2 negative, adherent, and phagocytic. We concluded that activated macrophages are able to inhibit T cell protein synthesis. In comparative studies, we found that the macrophage-dependent suppression of protein synthesis correlated with the capacity of the macrophage to suppress production of a lymphokine, migration inhibitory factor, by in vitro stimulated lymphocytes. The possibility that an early block of protein synthesis is one mechanism through which suppressor macrophages inhibit the immune response is discussed.