Inhibition of human lymphocyte proliferation by the nonmitogenic lectin wheat germ agglutinin.

DNA synthesis in human lymphocytes stimulated with mitogenic lectins (purified phytohemagglutinin, Con A, or pokeweed mitogen) or antigen (streptokinase-strep-todornase) is markedly inhibited by the nonmitogenic lectin wheat germ agglutinin (WGA). In contrast, WGA fails to inhibit DNA synthesis in cells stimulated with a calcium ionophore, A23187, or heavy metal mitogen, mercuric chloride. The inhibition by WGA in lectin or antigen stimulated cells is: 1) reversible with N-acetyl-D-glucosamine (NAG), a known inhibitor of WGA binding, 2) not associated with excessive cellular cytotoxicity, 3) dose related, occurring at concentrations greater than 15 micrograms/ml, 4) effective only with additions of WGA during the initial 24 to 48 hr of culture, and 5) present in cell populations highly enriched for either T or B cells. Interestingly, Con A-activated lymphocytes elaborate a soluble immune suppressor supernatant (SISS) that contains a factor(s) of m.w. 30 to 45,000 that binds to the same lymphocyte surface receptors as WGA and functionally recapitulates many of the inhibitory effects of WGA, including decreased mitogen or antigeninduced proliferation. These data suggest the presence of distinct glycoprotein membrane receptors for suppressor signals that contain NAG residues. The interaction of appropriate ligands with these receptors produces an effective intracellular signal that negatively modulates the immune response.