Inhibitory effect of cholera toxin on human natural cell‐mediated cytotoxicity and its augmentation by interferon

Abstract

Cholera toxin inhibits human natural cell-mediated cytotoxicity in a dose- and time-dependent manner. Pretreatment of lymphocytes with 10 ng/ml of cholera toxin for 2 h almost completely inhibited cytolysis. Interferon augmented human natural cell-mediated cytolysis, but when lymphocytes were pretreated with cholera toxin before interferon treatment, no enhancement of cytolysis occurred. Cholera toxin could inhibit the enhancement of cytolysis by interferon even when lymphocytes were treated with cholera toxin after 2 h interferon treatment. Cholera toxin subunit B which binds cell surface ganglioside galactosyl-N-acetylgalactosaminyl - [N-acetylneuraminyl] - galactosylglucosylceramide (GM1) without activating adenyl cyclase had no effect either on natural cytolysis or on the enhancement of natural cytolysis by interferon, suggesting that mere binding of cholera toxin to the cellular receptor was not enough to inhibit natural cell-mediated cytolysis. Cyclic adenosine 3',5'-monophosphate (cAMP) levels increased in cholera toxin-treated lymphocytes and the time course of cAMP accumulation was similar to that of cytotoxicity inhibition. Exogenous dibutyryl-cAMP (db-cAMP) and theophylline inhibited cytolysis, while exogenous dibutyryl cyclic guanosine 3',5'-phosphate (db-cGMP) enhanced cytolysis slightly, suggesting that the process of inhibition of human natural cell-mediated cytolysis was at least partly modulated by intracellular cyclic nucleotides.

Effects of β-adrenergic receptor activation, cholera toxin and forskolin on human natural killer cell function

“…The ADP-ribosylation of G,a by cholera toxin (CTX) produces the form of G,a which is able to activate adenylate cyclase [9,11,12]. CTX treatment of impure NK cells has been shown to inhibit NK-cell cytotoxicity [13,14]. However, since the effect of CTX was not studied in a highly purified population of NK cells, it was not known whether the effects of CTX were due to activation of a G,a, and a subsequent elevation of intracellular cAMP, in NK cells or to a secondary effect based on CTX affecting a G8a in some other cell type.…”

Ultrastructural localization of interferon receptors on the surfaces of cultured cells and erythrocytes

“…IFN treatment alters the interaction of cells with substances that utilize gangliosides as receptors, e.g., cholera and tetanus toxins, ricin, abrin, thyrotropin, and human chorionic gonadotropin (8,9,15,29); but there is conflicting evidence as to whether IFN inhibits the action of diphtheria toxin (DT) (1, 34,52), which is also thought to bind to glycoprotein receptors (40). On the other hand, cholera toxin treatment of cells alters the antiviral and cytotoxic activities of IFN (5, 14,16,17). Ligand binding studies have relied mainly upon quantitative biochemical analyses of an entire cell population.…”