Systemic delayed-type hypersensitivity to cholera toxin and a detoxified derivative.

The delayed-type hypersensitivity (DTH) response to cholera toxin (CT) and an immunopurified formalinized toxoid (TD) was studied in adult BALB/c mice. Intradermal injection of CT in non-immune animals produced substantial footpad oedema which interfered with the measurement of specific DTH but TD proved satisfactory as a challenge antigen. DTH to CT was induced by doses ranging from 0.1 to 10 micrograms, in complete Freund's adjuvant (CFA). The optimal reaction was primed for by 1 microgram CT. Doses of TD with an equivalent B subunit content were equally capable of inducing DTH as the holotoxin. The time-course of the footpad swelling revealed that the DTH response was biphasic. Histological examination showed that the initial swelling was due to tissue oedema and the subsequent increase in footpad thickness was associated with a mononuclear cell infiltrate at the site of antigen challenge. Adoptive transfer experiments were used to demonstrate that the DTH was antigen-specific and could be passively transferred by immune effector T cells. This is the first study to demonstrate an effector T cell response to CT. A role for T cell reactions in the intestinal mucosa must now be examined as a potential contributory mechanism in the prevention of choleraic diarrhoea.