Inhibition of mitogen stimulation of human peripheral blood leukocytes by Vibrio cholerae enterotoxin

It has been found that the enterotoxin (choleragen) of Vibrio cholerae, strain 569B, can interfere with Phytohemagglutinin-P, pokeweed mitogen and concanavalin A stimulation of human peripheral blood leukocytes. The viability of cultured cells was not affected by the toxin. The toxin does not interfere with stimulation by direct competition for mitogen receptor sites. The ability of choleragen to inhibit stimulation by mitogens declines with time after initiation of stimulation. The biologically inactive, spontaneously formed, derivative of choleragen, choleragemoid, did not inhibit mitogen stimulation. However, choleragenoid did block the inhibition of stimulation caused by choleragen. Choleragenoid did not block inhibition of mitogen stimulation by a lymphocyte chalone preparation indicating that a different mechanism may be involved with the chalone. Since the diverse biological effects of choleragen are all believed to result from its interaction with cell membrane receptors followed by activation of adenyl cyclase, the results add to evidence which suggests that increases in the intracellular concentrations of 3',5'-adenosine cyclic monophosphate diminishes the mitotic activity of cells.