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.
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D007165:Immunosuppression Therapy; D007930:Leucine / Q000378:metabolism; D007961:Leukocyte Migration-Inhibitory Factors / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D007961:Leukocyte Migration-Inhibitory Factors; D007930:Leucine