INDIRECT EFFECTS OF ORAL TOLERANCE IN MICE

Anti-DNP antibody formation resulting from intraperitoneal (i.p.) immu nization with DNP-KLH may be blocked by simultaneous (i.p.) injection of DNP-Ova or native Ova in mice orally tolerant to Ova, but not in no rmal mice. In Ova-tolerant mice the inhibition of anti-DNP antibody fo rmation also occurred when DNP-Ova and DNP-KLH were given by separate routes of immunization: subcutaneous (s.c.) and i.p. A second exposure to Ova by gastric intubation (gavage) or intravenous administration s imultaneously with i.p. immunization with DNP-KLH failed to inhibit an ti-DNP antibody formation. There was inhibition of responses to DNP-KL H i.p. by DNP-Ova given 24 h before, but not 24 h after, and in the Ov a-tolerant mice, addition of DNP-Ova only to the primary immunization with DNP-KLH inhibited secondary and tertiary responses to DNP-KLH in the absence of further exposures to DNP-Ova. These results suggest tha t the indirect effects of parenteral exposure of tolerant mice to the tolerated immunogen may inhibit unrelated immune responses. This inhib ition is not due to 'innocent bystanding' suppression, i.e., to inhibi tory cytokines provided locally by specific suppressor lymphocytes; it may derive from more durable perturbations of immune system.