Mechanisms and assessment of lectin-mediated mitogenesis.

The discovery of lectin-mediated mitogenesis by Nowell in 1960 stimulated interest in the properties of lectins while advancing knowledge of immunology. Although some lectins are polyclonal activators both in vitro and in vivo, others may display a broad range of activities toward human lymphocytes. Indeed, the same lectin (e.g., wheat germ agglutinin or Datura lectin) may be mitogenic, comitogenic, or antimitogenic, depending on the experimental conditions. An individual lectin may bind to several glycoproteins on the lymphocyte surface, resulting in interactions that may or may not be functionally relevant, and that may have opposing effects. Studies with lectins and with monoclonal antibodies (MAbs) have established that a surprisingly large variety of cell-surface molecules can influence the initiation and regulation of lymphocyte activation and proliferation. Interactions between lymphocytes and accessory cells are crucial; some signals are cell-mediated, but others depend on soluble cytokines. Mitogenic lectins presumably bind to the T-cell receptor complex and also promote a positive costimulatory signal leading to the synthesis of interleukin 2 and interleukin 2 receptors (IL-2R). Nonmitogenic, comitogenic, and antimitogenic lectin activities also probably act via accessory molecules involved in costimulation. Plant lectin-animal lymphocyte interactions presumably have no physiological significance, but it is suggested that the former mimics microbial superantigens, which may function in the colonization of host cells. Mitogenic stimulation of lymphocytes can be assessed in several ways. The standard technique measures [3H]-thymidine incorporation into DNA, but nonradioactive procedures are also available.