Antirheumatic E. coli extract OM-89 induces T cell responses to HSP60 and 70.
Oral administration of E. coli extract OM-89 is used in treating RA. It has been shown that immune reactivity to heat-shock proteins (hsp) is involved in immunomodulation of arthritis. We evaluated the postulated presence and immunogenicity of hsp's in OM-89. The effects of OM-89 in experimental arthritis were analyzed. Proliferative T cell responses to bacterial hsp60 and hsp70 were found in rats immunized with OM-89. And conversely, immunization with hsp antigens induced OM-89-specific T cell responses. Hsp70 (DnaK) was found to be a major immunogenic constituent of OM-89. Parenteral immunization with OM-89 reduces resistance to adjuvant arthritis (AA), whereas oral administration protects against AA. Given the arthritis inhibitory effect of oral OM-89 in AA our findings suggest peripheral tolerance induced by hsp-specific regulatory T cells as a mode of action for OM-89 as an arthritis suppressive oral drug.
Wendling
U
U
Institute for Infectious Diseases and Immunology, Utrecht University, The Netherlands.
Bloemendal
A
A
Van Der Zee
R
R
Rutten
V P
VP
Van Kooten
P J
PJ
Farine
J C
JC
Van Eden
W
W
D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D018834:Chaperonin 60 / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009161:Mycobacterium / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D018501:Antirheumatic Agents; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D007166:Immunosuppressive Agents; C050501:OM 89