SUPPRESSION OF ADJUVANT ARTHRITIS IN RATS BY INDUCTION OF ORAL TOLERANCE TO MYCOBACTERIAL 65-KDA HEAT-SHOCK PROTEIN

Oral administration of mycobacterial 65-kDa heat shock protein (HSP) g iven daily for 5 days prior to immunization with Mycobacterium tubercu losis (Mt) suppressed the development of adjuvant arthritis (AA) in ra ts. AA was significantly suppressed by 30 and 300 mu g HSP and variabl y by 0.3, 3 mu g or 1 mg. Histological analysis of joint samples obtai ned from control and test rats confirmed the suppression of AA in the fed group. Feeding Mt or hen egg lysozyme (HEL) failed to affect AA. i ndicating that the suppression was HSP specific. The oral administrati on of 30 mu g HSP decreased both delayed-type hypersensitivity (DTH) r eactions and proliferative responses to HSP and Mt. In addition, the p roliferation of lymph node cells (LNC) from Mt-sensitized rats was inh ibited by the addition of spleen cells (SPC) from HSP-fed animals, pos sibly by the secretion of transforming growth factor (TGF)-beta. Splee n cells obtained from tolerized donors were capable of transferring th e tolerance to naive recipients. These results demonstrate that feedin g HSP is an effective way to suppress AA and that the suppression of A A may be mediated by regulatory T cells generated following oral admin istration of mycobacterial 65-kDa HSP.