Supernatants of murine spleen cells activated in MLC contain both MIF and a factor which induces plasminogen activator secretion by macrophages. These activities are not found in supernatants of unstimulated T cells in control (syngeneic) cultures. Because no plasminogen activator or fibrinolytic activity was detected in the lymphocyte supernatants directly, but appeared when supernatants were added to macrophages, we infer that production of this activity is induced in macrophages by an inducer of plasminogen activator (IPA).

IPA and MIF activities are first detected after 24 hr of MLC; peak activity occurred on day 3. Both factors eluted from Bio-Gel P-100 columns in the range of Kd 0.15 to 0.25 (m.w. range 25,000 to 60,000 daltons).

Production of both factors in this system required the presence of T cells. In experiments using anti-Ly 1 and anti-Ly 2,3 sera + C, it was observed that both the Ly 1 (helper-type) and Ly 2,3 (cytotoxic/suppressor-type) T cell subpopulations produced each mediator. It is likely that the production of mediators by individual T cell subsets in vivo is not restricted by their intrinsic capabilities, but rather by factors which determine their activation. These results point to the possible importance of both T cell subpopulations in activating macrophages, and indirectly in aspects of tissue injury resulting from cell-mediated immune reactions involving protease activation.

Since IPA correlated with MIF in terms of activity (0.78 coefficient of correlation), kinetics of production, gel filtration characteristics, and production by T cell subsets, and because the assay for plasminogen activator is a sensitive and reproducible one, it should be increaseingly useful in in vitro studies of cell-mediated immunity.

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This work was supported by United States Public Health Service Grants AI07118, 10704, and 12975; a grant from the Rockefeller Foundation; and the Jane Coffin Childs Memorial Fund for Medical Research.

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