Parenteral immunization causes antigen-specific cell-mediated suppression of an intestinal IgA response

Rats immunized s.c. with cholera toxin (CT) or toxoid (CTd) show antigen-specific suppression of the jejunal IgA anti-CT response to subsequent enteric doses of CT. We determined whether this effect was partly cell-mediated and studied the suppressor cell response involved. Spleen cells from s.c.-immunized rats suppressed the jejunal anti-CT response in adoptive recipients when cell transfer was at, or 4 days before, intraduodenal priming with CT. Transferred suppression was antigen-specific, and the suppressor cells were nylon wool-nonadherent. Increasing the s.c. dose of CT from 0.1 to 40 micrograms, and the interval between immunization and cell harvest from 2 to 16 wk, each increased the suppressive effect of a constant spleen cell inoculum. After s.c. immunization, suppressor cells were present in the spleen within 1 to 2 wk, among TDL within 4 to 8 wk, and in Peyer's patches and thymus within 8 to 16 wk; this sequence suggested they arose in the spleen and later migrated to mucosae and the thymus. Prior splenectomy did not alter the suppressive effect of s.c. CT, however, nor did it prevent suppressor cell appearance among TDL, indicating that suppressor cells also arose from nonsplenic sites. Transferred suppressor cells acted by interfering with the development of specific immunologic memory within Peyer's patches during enteric priming; transfer of suppressor cells at the time of enteric boosting had no effect upon the secondary mucosal anti-CT response. We conclude that the suppressive effect of s.c. immunization on a specific mucosal IgA response is due largely to the action of systemically derived suppressor cells upon the primary mucosal immune response within Peyer's patches. This sequence resembles the mirror image of oral tolerance, which involves the suppression of systemic IgG and IgM responses by suppressor cells that arise in Peyer's patches and migrate to the spleen after antigen feeding.