The immunological consequences of feeding cholera toxin. I. Feeding cholera toxin suppresses the induction of systemic delayed-type hypersensitivity but not humoral immunity.

Immunization of adult BALB/c mice with 1 microgram cholera toxin (CT) in complete Freund's adjuvant (CFA) induced both humoral (IgG and IgA) and cell-mediated (DTH) immunity. Although an immunopurified, formalinized, cholera toxoid (TD) in CFA was inferior to the native holotoxin at inducing antitoxin antibodies, both cholera-derived antigens were equally immunogenic for specific DTH. When mice were fed either 1 microgram CT or 5 microgram TD 1 week before immunization, the induction of DTH was inhibited but the development of specific antibody was the same as in sham-fed controls. A feed of 10 micrograms CT not only suppressed the induction of DTH but also enhanced the IgG antitoxin responses measured 1 week after immunization. A dose of TD (50 micrograms), with a similar cholera toxin B subunit content, also induced oral tolerance for DTH but had no effect on the subsequent development of humoral immunity. The smallest doses of CT or TD fed (0.1 microgram and 0.5 microgram, respectively) failed to affect the development of either limb of the systemic immune response. These results suggest that oral tolerance for DTH is not consequent upon the metabolic actions of CT but that stimulation of systemic antibodies after enteric administration may be. Pretreating mice with cyclophosphamide (Cy) (100 mg/kg) before feeding CT abrogated the induction of oral tolerance for DTH but had no effect on humoral immunity, suggesting that suppressor T cells may be responsible for the induction of oral tolerance in these animals.