SPECIFIC AND LONG-LASTING PROTECTION FROM COLLAGEN-INDUCED ARTHRITIS AND OIL-INDUCED ARTHRITIS IN DA RATS BY ADMINISTRATION OF IMMUNOGENS

DA rats develop transient arthritis after subcutaneous immunization with adjuvant-oil, while chronic arthritis and collagen autoreactivity ensues when collagen is added to the oil. We show here that DA rats can be protected from oil-induced arthritis (OIA) and rat collagen-induced arthritis (rCIA) by addition of antigen to these arthritogenic inocula. We have investigated this remarkable phenomenon and demonstrate that both foreign and self antigens can be protective, apparently provided-they are immunogenic; hence HSP-65kDa, ovalbumin, rat myelin basic protein, rat IgG and bovine albumin are effective while rat albumin is not. This protection is long-lasting and disease-specific because rats protected from rCIA resist a later attempt to induce arthritis, but not experimental autoimmune encephalomyelitis (EAE). Protection from rCIA depends neither on the blocking of humoral autoreactivity to collagen nor on a change in the isotype profile of anti-collagen antibodies. We demonstrate that immunogens can also be protective when injected intraperitoneally only a few days before onset of arthritis. Our results indicate that protection is mediated through bystander immune reactions towards the co-immunized antigen and that the arthritogenicity of a given provocation, be it adjuvants, microbes or autoantigens, may be a complex net result of arthritogenic and contra-arthritogenic immune reactions.