Clonal Anergy Is a Potent Mechanism of Oral Tolerance in the Suppression of Acute Antigen-Induced Arthritis in Rats by Oral Administration of the Inducing Antigen

The effects of oral administration of ovalbumin (OVA) on acute OVA-induced arthritis (OIA) in rats, which is mediated by Arthus reaction to the antigen in the joint space, were investigated. The oral administration of OVA before immunization with OVA significantly suppressed the development of acute OIA in a dose-dependent manner, in accordance with decreases in both thein vivoanti-OVA IgG antibody production andin vitrolymphocyte proliferative responses to OVA. These results were shown in both the single high-dose (200 mg × 1) or the multiple low-dose (200 μg × 5) feeding protocols.In vitrostudy showed that rat IL-2 could reverse the reduced OVA-specific lymphocyte proliferative responses. The spleen cells obtained from OVA-feeding, unprimed rats neither adoptively transferred the suppression to naive recipient rats nor suppressed thein vitrolymphocyte proliferation. These results demonstrate that the acute OIA can be suppressed by the induction of oral tolerance (OT) to OVA, and strongly suggest that the OT was due to clonal anergy of antigen-reactive T lymphocytes, not the active suppression by OVA-specific regulatory cells.