T cell inhibitor secreted by macrophages and endothelial cells

On stimulation with lipopolysaccharide (LPS), normal human macrophages (M phi) and endothelial cells (EC) produced factors which inhibited interleukin 2 (IL-2)-dependent lymphocyte proliferation and PHA plus interleukin 1 (IL-1)-dependent mouse thymocyte proliferation but not IL-1-dependent human fibroblast proliferation, suggesting that they were inhibitors of the IL-2 response. In addition, these factors inhibited the production of IL-2 by normal human peripheral blood mononuclear cells (PBMC). The factors also inhibited PBMC proliferation in response to PHA and concanavalin (Con A) but did not inhibit the proliferation of EC, U937 cells, or Epstein-Barr virus-transformed B cells. On Sephadex G200 gel filtration, the inhibitory factors from both M phi and EC were detected almost entirely in a 130- to 150-kDa fraction, but active material was also detected in a 15- to 20-kDa fraction. On isoelectric chromatofocusing of the 130- to 150-kDa fraction, inhibitory activity was associated with fractions eluted at three isoelectric points, pH 7.0, 5.4, and 4.8. The isoelectric fractions isolated from M phi and EC showed similar patterns of inhibition. When 130- to 150-kDa fractions from Sephadex G200 of the M phi and EC supernatants were treated with an antibody against a macrophage-derived suppressor factor produced by the human monocytic leukemia cell line THP-1, the activity of both fractions was neutralized. The above findings suggest that normal M phi and EC secrete an identical or closely related inhibitor of IL-2 synthesis and IL-2 response, and this inhibitor regulates these IL-2-related functions by a suppressive action on the T lymphocyte.