Indirect Effects of Oral Tolerance in Mice

Abstract

Anti-DNP antibody formation resulting from intraperitoneal (i.p.) immunization 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 normal mice. In Ova-tolerant mice the inhibition of anti-DNP antibody formation 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 simultaneously with i.p. immunization with DNP-KLH failed to inhibit anti-DNP antibody formation. There was inhibition of responses to DNP-KLH i.p. by DNP-Ova given 24 h before, but not 24 h after, and in the Ova-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 that the indirect effects of parenteral exposure of tolerant mice to the tolerated immunogen may inhibit unrelated immune responses. This inhibition is not due to 'innocent bystanding' suppression, i.e., to inhibitory cytokines provided locally by specific suppressor lymphocytes; it may derive from more durable perturbations of immune system.

Indirect Effects of Oral Tolerance Cannot be Ascribed to Bystander Suppression

“…We had already shown [28] that the indirect effects do not occur when the tolerated antigen is injected (both in the primary and secondary immunization) 24 h after the unrelated antigen. The reverse is not true, i.e.…”

“…However, we [27][28][29][30] and others [34][35][36] have demonstrated that injection of a tolerated antigen results in inhibition of antibody response to a second unrelated antigen injected simultaneously. We have called this phenomenon indirect effects of the exposure to tolerated proteins.…”

“…However, the addition of tolerated antigens to immunizing doses of unrelated antigens blocks antibody responses to these unrelated antigens, a phenomenon which we have called indirect effects of oral tolerance [28][29][30]. The present work was undertaken to determine whether the inhibition of antibody responses triggered by immunization with tolerated antigens (i.e.…”

Tolerância oral: uma nova perspectiva no tratamento de doenças autoimunes

“…Esse fenôme-no sugere mecanismo de supressão cruzada, já que a exposição parenteral a um imunógeno tolerizado pode ocasionar alterações no sistema imune como uma inibição das respostas imunes a um imunó-geno não relacionado. Em ratos tolerizados pela via oral à Ova (Ovalbumina), a injeção de tal substância foi capaz de inibir a imunização encefalitogênica com MBP (proteína básica de mielina) 22 . A supressão cruzada é transferível não necessitando que o autoantígeno alvo seja utilizado, e sim que a proteína administrada seja capaz de induzir células Th2 à produção de citocinas supressoras no órgão alvo 23 .…”

Immaturity, Ageing and Oral Tolerance

“…We found that parenteral injections of the tolerated antigen into orally tolerant mice are able to inhibit the concomitant initiation of several different immunological phenomena, such as antibody responses to unrelated antigens [66][67][68] or parental to F1 graftvs.-host [69]. One injection of small amounts (10-20 mg) proteins present in regular mouse chow, such as zein, as well as selfcomponents, such as mouse fibrinogen, may be used to block antibody responses to dinitrophenyl-haemocyanin [67].…”