Local and systemic tolerance to orally administered dinitrochlorobenzene is not broken by cholera toxin

It is widely acknowledged that oral administration of many antigens induces antigen-specific systemic tolerance. In this study we tested the hypothesis that oral administration of a low dose of dinitrochlorobenzene (DNCB) could induce local tolerance in the absence of systemic tolerance. We also hypothesized that the mucosal adjuvant cholera toxin (CT), which prevents the induction of local and systemic tolerance to coadministered antigens, would be unable to break an established tolerance to an orally administered antigen.

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 DNCB. This pretreatment was followed by parenteral or oral administration of dinitrophenyl (DNP)-carrier protein conjugates.

As anticipated, the high DNCB dose induced systemic tolerance, as evidenced by depressed delayed type hypersensitivity responses to DNCB and reduced serum IgG anti-DNP responses. Oral pretreatment with the high dose of DNCB also induced local tolerance, as indicated by reduced fecal IgA and IgG anti-DNP responses. Conversely, oral pretreatment with the low dose of DNCB induced only local, not systemic tolerance. In addition, CT was incapable of breaking the preexisting tolerance induced by oral DNCB pretreatment.

This study and others support the notion that the mucosal arm of the immune system is more sensitive to the 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.