International Immunology, Vol 10, 1613-1622, Copyright © 1998 by Oxford University Press
GE Osman, S Cheunsuk, SE Allen, E Chi, HD Liggitt, LE Hood and WC Ladiges
Animal models of autoimmune diseases have been instrumental in advancing
our understanding of autoimmunity in humans. Collagen-induced arthritis in
mice is an autoimmune disease model of rheumatoid arthritis, which is MHC
class II restricted and CD4 T cell dependent. To better understand the
fundamental role of T cells in arthritis, we have generated a transgenic
mouse carrying the rearranged Valpha11.1 and Vbeta8.2 TCR chain genes
isolated from a type II collagen (CII)- specific T cell hybridoma. Cell
surface analysis indicated that Vbeta8.2 chain was expressed on the surface
of nearly all peripheral T cells. Analysis of T cell subsets in transgenic
mice revealed a profound skewing in peripheral T cells towards the CD4
population. Although peripheral T cells were not tolerant to CII and
responded to CII stimulation in vitro, transgenic mice did not develop
spontaneous arthritis. However, a rapid onset of arthritis with severe
clinical signs was detected in transgenic mice after immunization with CII
in complete Freund's adjuvant. Histological analysis of inflamed joints
showed a great resemblance to arthritic joints in man. This unique
transgenic mouse model provides valuable insights into the mechanism of
arthritis and into potential specific immune interventions.
ARTICLES
Expression of a type II collagen-specific TCR transgene accelerates the onset of arthritis in mice
Department of Molecular Biotechnology, University of Washington School of Medicine, Seattle 98195, USA.
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