Cholera toxin inhibits resting human T cell activation via a cAMP-independent pathway.

摘要: The catalytic subunit of cholera toxin (CT) can chemically modify the alpha polypeptides certain G-binding proteins and thus alter their function. In order to study involvement CT-sensitive G in T cell activation, we have utilized CT an vitro system which purified, resting human peripheral cells are activated by anti-CD3 antibodies rIL-2. Perturbation TCR/CD3 molecular complex causes changes membrane phospholipids induces a rise cytoplasmic Ca2+. These events, however, insufficient allow progression into cellular proliferation addition IL-2 is required. Under these conditions, treatment with low concentration (2 ng/ml) significant inhibition anti-CD3-induced calcium event as well plus IL-2-stimulated proliferation. our experimental both intracellular Ca2+ elevation requires complex. This supported observation that does not inhibit either triggered ionomycin PMA or influx induced ionophore. data suggest TCR/CD3-mediated activation acts at point between perturbation generation view ability activate protein stimulates adenyl cyclase (G s), it possible effect on secondary cAMP. However, measurement cAMP levels early after later time points, when maximal, reveals lack cyclic nucleotide accumulation. presented consistent interpretation CT-mediated caused modification directly indirectly associated triggering via also this s probably represents yet unidentified moiety one several been recently described regulators phospholipase C activation.