LOCAL AND SYSTEMIC TOLERANCE TO ORALLY-ADMINISTERED DINITROCHLOROBENZENE IS NOT BROKEN BY CHOLERA-TOXIN

Background: It is widely acknowledged that oral administration of many antigens induces antigen-specific systemic tolerance. In this study w e tested the hypothesis that oral administration of a low dose of dini trochlorobenzene (DNCB) could induce local tolerance in the absence of systemic tolerance. We also hypothesized that the mucosal adjuvant ch olera toxin (CT), which prevents the induction of local and systemic t olerance to coadministered antigens, would be unable to break an estab lished tolerance to an orally administered antigen. Methods: Tolerance was induced in BALB/c mice by oral administration of either a high (5 .0 mg) or a low (0.05 mg) oral dose of the contact-sensitizing agent D NCB. This pretreatment was followed by parenteral or oral administrati on of dinitrophenyl (DNP)-carrier protein conjugates, Results: As anti cipated, the high DNCB dose induced systemic tolerance, as evidenced b y depressed delayed type hypersensitivity responses to DNCB and reduce d serum IgG anti-DNP responses. Oral pretreatment with the high dose o f DNCB also induced local tolerance, as indicated by reduced fecal IgA and IgG anti-DNP responses. Conversely, oral pretreatment with the lo w dose of DNCB induced only local, not systemic tolerance. In addition , CT was incapable of breaking the preexisting tolerance induced by or al DNCB pretreatment. Conclusion: This study and others support the na tion that the mucosal arm of the immune system is more sensitive to th e induction of tolerance than the systemic arm, and that CT may not be an effective adjuvant for antigens to which the mucosal immune system has previously been exposed.