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.
Lorentzen
J C
JC
Department of Rheumatology, Karolinska Institute, Stockholm, Sweden.
Erlandsson
H
H
Müssener
A
A
Mattsson
L
L
Kleinau
S
S
Nyman
U
U
Klareskog
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000627:therapeutic use*; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000627:therapeutic use; D003094:Collagen / Q000276:immunology / Q000633:toxicity*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000627:therapeutic use; D008297:Male; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000627:therapeutic use; D009821:Oils / Q000633:toxicity*; D010047:Ovalbumin / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000627:therapeutic use
D000941:Antigens; D001426:Bacterial Proteins; D018834:Chaperonin 60; D007074:Immunoglobulin G; D004676:Myelin Basic Protein; D009821:Oils; C074119:heat-shock protein 65, Mycobacterium; D012710:Serum Albumin, Bovine; D010047:Ovalbumin; D003094:Collagen; D018833:Chaperonins