Abstract
Adjuvant arthritis (AA) is a frequently used model of experimental arthritis. Because of its histopathology, which is reminiscent of rheumatoid arthritis in humans, AA is used as a model for the development of novel anti-inflammatory drugs. Recently, it has become evident that AA is a typical T-cell-mediated autoimmune condition. Therefore, novel immunotherapies targeted to T cells can be developed in this model. Analysis of responding T cells in AA have now led to the definition of various antigens with potential relevance to arthritis, including human arthritic conditions. One such antigen defined in AA is the 60kD heat shock protein. Both T-cell vaccination approaches and active antigen immunizations and antigen toleration approaches have turned out to be effective in suppressing AA.
Highlights
Adjuvant arthritis (AA) is a frequently used model of experimental arthritis
Later the mycobacterial antigen was defined as the mycobacterial heat shock protein 60, and the epitope of the arthritogenic T cell turned out to be nonconserved with a limited sequence homology with a rat proteoglycan link-protein sequence
Careful analyses of differential T-cell responsiveness of whole mycobacteria- (AA induction protocol) versus mycobacterial hsp60- immunized rats have pointed out that the arthritis inductive capacity of whole mycobacteria does coincide with dominant responses directed to the mimicry epitope 180-188.9 This is not the case when the hsp[60] protein is used for immunization
Summary
VAN EDEN the nonantigenic synthetic adjuvant avridine (CP20961).[3] Apparently, this single bacterial epitope, which resembles a (so far not identified) self epitope at the site of inflammation, is capable of inducing regulatory mechanisms of peripheral tolerance. The success of this regimen in suppressing disease, and especially in the case of nonmicrobially induced disease, seems to support the possibility that this microbial epitope has a unique relationship with a disease critical self-antigen in the joint. Immunization experiments in mice and rats using hsp[60] proteins or their derivative peptides have never led to induction of arthritis. For the smaller subunit of the hsp[60] complex (GroES of Escherichia coli of 10kD molecular weight), arthritis protective potential has been documented
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