Increased division of αβ TCR⁺ and γδ TCR⁺ intestinal intraepithelial lymphocytes after oral administration of cholera toxin

Cholera toxin (CT) or its subunits were given orally to mice and division of intestinal intraepithelial lymphocytes (IEL) in vivo measured by double immunofluorescence using 5-bromo-2′-deoxyuridine (BRdU) and membrane αβ T-cell receptors (TCR) or γδ TCR⁺ staining in frozen sections. Cholera toxin (10 μg) produced a two- to eightfold-increase in the uptake of BRdU in αβ TCR⁺ IEL in the duodenum and a two- to fivefold increase in γδ TCR⁺ IEL in the ileum. Increased uptake of BRdU was also seen after a dose of 100 μg of CT, but this dose was also associated with the loss of αβ TCR⁺ IEL and γδ TCR⁺ IEL in the duodenum. CT-A and CT-B subunit produced increased BRdU incorporation by αβ TCR⁺ in the duodenum and by γδ TCR⁺ IEL in the ileum. Cholera toxin therefore appears to be mitogenic for IEL, probably due to an indirect mechanism.