Regulation of lymphocyte proliferation by soluble products released by stimulated human lymphocytes

Human lymphocytes pulsed with phytothaemagglutinin (PHA) release mitogenic factors and other lymphokines upon subsequent incubation in fresh medium. Such active supernatants (SUPs) were assayed for their capacity to modify the DNA synthetic response of human lymphocytes exposed to various mitogenic stimuli. Both non-fractionated peripheral lymphocytes and preparations of fractionated T cells were stimulated by active SUPs to DNA synthesis. In contrast, active SUPs reduced the responses of lymphocytes to allogeneic cells, PPD tuberculin and PHA. These reductions were most evident at the end of the culture periods. The results suggest that soluble products released by stimulated lymphocytes activate suppressor lymphocytes which inhibit proliferative responses of lymphocytes.