Abstract
The antigens that trigger the pathogenic immune response in rheumatoid arthritis (RA) remain unknown. Until recently it was assumed that either viral or microbial antigens, or joint-specific antigens were the target of arthritogenic T and B lymphocytes in RA. Consequently, murine models of arthritis are induced by immunization with either joint-specific antigens such as type II collagen or microbial products such as streptococcal cell wall. In the K/BxN T-cell receptor transgenic mouse model arthritis is caused by a systemic autoimmune response to the ubiquitously expressed glycolytic enzyme glucose-6-phosphate isomerase (G6PI). The autoreactive transgenic T cells recognize G6PI and provide help for the production of arthritogenic IgG antibodies against G6PI. More recently it was shown that G6PI immunization induces severe symmetrical peripheral polyarthritis in genetically unaltered DBA/I mice. In that model CD4+ T cells are necessary not only for the induction but also for the effector phase of arthritis. Here we review the pathomechanisms that lead from systemic autoreactivity to arthritis in these models, consider the relevance of anti-G6PI immune reactivity for RA, and discuss the insights into the pathogenesis of RA and possibly other autoimmune conditions that can be gained from these models.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antibody Specificity
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Arthritis, Experimental / enzymology
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Arthritis, Experimental / etiology
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Arthritis, Experimental / immunology*
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Arthritis, Rheumatoid / immunology
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Autoantibodies / immunology*
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Autoantigens / immunology*
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Autoimmune Diseases / enzymology
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Autoimmune Diseases / etiology
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Autoimmune Diseases / immunology*
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B-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / immunology
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Cell Wall / chemistry
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Cell Wall / immunology
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Collagen Type II / immunology
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Collagen Type II / toxicity
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Complement System Proteins / immunology
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Crosses, Genetic
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Glucose-6-Phosphate Isomerase / immunology*
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Histocompatibility Antigens Class II / immunology
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Humans
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Immunization
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Immunization, Passive
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Immunoglobulin G / immunology
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Interleukin-1 / physiology
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Mast Cells / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Mice, Inbred NOD
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Mice, Transgenic
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Nervous System Autoimmune Disease, Experimental / etiology
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Nervous System Autoimmune Disease, Experimental / immunology
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Neutrophils / immunology
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
Substances
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Autoantibodies
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Autoantigens
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Collagen Type II
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Histocompatibility Antigens Class II
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I-Ak antigen
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Immunoglobulin G
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Interleukin-1
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Receptors, Antigen, T-Cell
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Complement System Proteins
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Glucose-6-Phosphate Isomerase