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)
A. Bloemendal et al., 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), Clinical and experimental immunology, 110(1), 1997, pp. 72-78
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.