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-ind uced arthritis (OIA) in rats, which is mediated by Arthus reaction to the antigen in the joint space, were investigated. The oral administra tion of OVA before immunization with OVA significantly suppressed the development of acute OIA in a dose-dependent manner, in accordance wit h decreases in both the in vivo anti-OVA IgG antibody production and i n vitro lymphocyte proliferative responses to OVA. These results were shown in both the single high-dose (200 mg x 1) or the multiple low-do se (200 mu g x 5) feeding protocols. In vitro study showed that rat IL -2 could reverse the reduced OVA-specific lymphocyte proliferative res ponses. The spleen cells obtained from OVA-feeding, unprimed rats neit her adoptively transferred the suppression to naive recipient rats nor suppressed the in vitro lymphocyte proliferation. These results demon strate that the acute OIA can be suppressed by the induction of oral t olerance (OT) to OVA, and strongly suggest that the OT was due to clon al anergy of antigen-reactive T lymphocytes, not the active suppressio n by OVA-specific regulatory cells. (C) 1997 Academic Press