The immunological consequences of feeding cholera toxin. II. Mechanisms responsible for the induction of oral tolerance for DTH.

The mechanisms behind the induction of oral tolerance after feeding cholera toxin (CT) were examined using cell and serum transfer protocols. The feeding of CT or cholera toxoid (TD) induced a splenic cell capable of inhibiting the induction of systemic delayed-type hypersensitivity (DTH) but not humoral immunity. Depletion studies showed that this cell was Thy-1.2 positive. Transfer experiments suggested that suppressor cell activity was present in the mesenteric lymph nodes (MLN) and spleens of donor mice 1 week but not 3 days after feeding CT. When spleen cells were transferred to syngeneic recipients at various times after immunization, they were more effective at inhibiting systemic DTH when transferred within a short time of immunization. If the cells were transferred 6 days after immunization they no longer suppressed the development of DTH, which suggested that they inhibit the afferent limb of this immune response. This has been confirmed by the failure of a tolerogenic dose of CT, administered by gavage, to suppress the activity of mature effector TDTH cells. Serum collected 1 hr after feeding CT also suppressed the induction of systemic DTH. However, the tolerogenic activity of CT-fed serum was abrogated by the pretreatment of recipients with cyclophosphamide (Cy) (100 mg/kg), suggesting that this activity is mediated through the induction of suppressor cells. Transfer of fed serum, however, did not induce the splenic suppressor cell described above and we would suggest that several mechanisms may operate in the mucosal regulation of systemic DTH.