Expression of a type II collagen-specific TCR transgene accelerates the onset of arthritis in mice.

Abstract:

: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.

journal_name

Int Immunol

journal_title

International immunology

authors

Osman GE,Cheunsuk S,Allen SE,Chi E,Liggitt HD,Hood LE,Ladiges WC

doi

10.1093/intimm/10.11.1613

subject

Has Abstract

pub_date

1998-11-01 00:00:00

pages

1613-22

issue

11

eissn

0953-8178

issn

1460-2377

journal_volume

10

pub_type

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