EXPERIMENTAL IMMUNIZATION WITH ANTIRHEUMATIC BACTERIAL EXTRACT OM-89 INDUCES T-CELL RESPONSES TO HEAT-SHOCK-PROTEIN (HSP)60 AND HSP70 - MODULATION OF PERIPHERAL IMMUNOLOGICAL-TOLERANCE AS ITS POSSIBLE MODE OF ACTION IN THE TREATMENT OF RHEUMATOID-ARTHRITIS (RA)

OM-89 is a bacterial (Escherichia coli) extract used for oral administ ration in the treatment of RA. Given the evidence that immunity to bac terial heat shock antigens plays a critical role in the immunomodulati on of arthritis and possibly inflammation in general, the purpose of t he present studies was to evaluate the presence and immunogenicity of hsp in OM-89. Furthermore, we studied the effects of OM-89 in an exper imental arthritis, where hsp are known to have a critical significance in disease development, in rats immunization with OM-89 was found to lead to proliferative T cell responses to hsp60 and hsp70 of both E. c oli and mycobacterial origin. Conversely, immunization with hsp antige ns was also found to induce T cell reactivity specific for OM-89, Base d on this and the antigen specificity analysis of specific T cell line s, hsp70(DnaK) turned out to be one of the major immunogenic constitue nts of OM-89. Parenteral immunization with OM-89 was found to reduce r esistance to adjuvant arthritis (AA), whereas oral administration was found to protect against AA. Given the arthritis-inhibitory effect of oral OM-89 in AA, it is possible that peripheral tolerance is induced at the level of regulatory T cells with specificity for hsp. This may also constitute a mode of action for OM-89 as an arthritis-suppressive oral drug.