The Immunogenetic Basis of Collagen Induced Arthritis in Mice: An Experimental Model for the Rational Design of Immunomodulatory Treatments of Rheumatoid Arthritis
Elucidating the genetic influences and immunological processes involved in the induction and pathogenesis of rheumatoid arthritis (RA) has been an area of intense investigation over the past two decades. During this period, various experimental animal models of RA have been studied which have contributed greatly to our basic understanding of this disease. One model of particular interest is the mouse model of collagen induced arthritis (CIA). Following the initial description of the model in rats,1 the successful induction of CIA in mice was achieved by Courtenay et al.2 CIA is usually induced by the intradermal injection of heterologous or homologous type II collagen (CII) in complete Freund’s adjuvant.3,4 Both T and B cell reactivity to CII is detected and, approximately 4–6 weeks post-immunization, mice develop a polyarthritis initially characterized by erythema and edema followed by joint distortion and, in some cases, culminating in joint ankylosis.5 Histologic examination of afflicted paws from mice with CIA reveals marked synovial proliferation, pannus formation and subsequent joint destruction with replacement by mononuclear cells.6 These clinical and histopathologic features of CIA strongly resemble those observed in human RA. Of particular importance has been the fact that the availability of numerous inbred mouse strains has enabled scientists to undertake a systematic and detailed analysis of the genetic factors contributing to this disease. Thus, understanding the immunogenetic characteristics of murine CIA strengthens the potential of this model for developing specific immune intervention strategies in human RA.
KeywordsCollagen Induce Arthritis Major Histocompatibility Complex Molecule Human Rheumatoid Arthritis Trimolecular Complex Major Histocompatibilty Complex
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