Concanavalin A inhibits the effector phase of specific cytotoxicity.
The effects of concanavalin A (Con A) on the effector phase of specific and nonspecific cytotoxicity were studied. The addition of the lectin to the cytotoxicity assay resulted in inhibition of specific cytotoxicity and induced the lysis of nonspecific targets only when the lectin was added after the target cells. Preincubation of the effector cells with the ligand strongly inhibited specific cytotoxicity and did not induce nonspecific cytotoxicity. However, preincubation of the target cells with Con A before addition to the assay had no effect on the specific lysis and strongly facilitated the lysis of nonspecific targets. The inhibitory effect was not due to the agglutinating property of the lectin, since another agglutinogenic and non-mitogenic lectin (Helix pomatia) did not inhibit cytotoxicity. Induction of effector-to-effector killing seemed unlikely, since the addition of Con A to 51Cr-labelled effector cells did not significantly enhance the release of isotope. The inhibitory effect could be reversed by a subsequent incubation of the Con A-treated effectors with alpha-methyl-d-mannoside. We suggest that Con A inhibits specific alloreactive cytotoxicity by blocking the antigen-binding receptors of T cells and induces nonspecific cytotoxicity by already activated cytotoxic T lymphocytes (CTLs) by binding to the major histocompatibility complex (MHC) antigens of the targets and creating structures mimicking allogenic MHC products that will be recognized by CTLs via the antigen-binding receptors.
D000818:Animals; D003208:Concanavalin A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006372:Helix, Snails; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D037102:Lectins / Q000494:pharmacology; D008766:Methylmannosides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA
D007166:Immunosuppressive Agents; D037102:Lectins; D008766:Methylmannosides; D003208:Concanavalin A