Evidence that Nonspecific Inhibitors Are Induced by Soluble Products of Activated Human Lymphocytes

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Abstract
Cultures of lymphocytes stimulated by polyclonal mitogens or specific antigens exhibit an initial wave of cell proliferation followed by a decline which has been explained by the activation of suppressor T cells. This article presents the first results aiming at testing the possibility that the suppressor cells are activated by soluble products released by stimulated lymphocytes. It was found that the supernatants of PHA-activated human lymphocytes stimulate lymphocytes to DNA synthesis with peak responses occurring on day 5 independent of the cell concentration in the cultures. In contrast, the kinetics of lymphocyte responses to phytomitogens or in the mixed lymphocyte culture were found to be dependent on cell concentration; peak responses were delayed at decreasing cell concentrations. The results support the view that certain lymphokines released in stimulated lymphocyte cultures induce suppressor cells and that biologically active concentrations are reached earlier at high cell densities.