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Publication : Naive transgenic T cells expressing cartilage proteoglycan-specific TCR induce arthritis upon in vivo activation.

First Author  Berlo SE Year  2005
Journal  J Autoimmun Volume  25
Issue  3 Pages  172-80
PubMed ID  16257179 Mgi Jnum  J:132543
Mgi Id  MGI:3776219 Doi  10.1016/j.jaut.2005.09.017
Citation  Berlo SE, et al. (2005) Naive transgenic T cells expressing cartilage proteoglycan-specific TCR induce arthritis upon in vivo activation. J Autoimmun 25(3):172-80
abstractText  Proteoglycan (PG)-induced arthritis (PGIA), a murine model for rheumatoid arthritis (RA), is driven by antigen (PG)-specific T and B cell activation. In order to analyze the pathogenic role of antigen-specific T cells in the development of autoimmune arthritis, we have generated a transgenic (Tg) mouse. The CD4(+) T cells of this TCR-5/4E8-Tg line express a functional T cell receptor (TCR) composed of the Valpha1.1 and Vbeta4 chains with specificity for the dominant arthritogenic T cell epitope of human cartilage PG. Adoptive transfer of naive TCR-5/4E8-Tg cells induced arthritis with severe clinical symptoms in syngeneic immunodeficient BALB/c.RAG2(-/-) mice. In vivo activation of TCR-5/4E8-Tg CD4(+)Vbeta4(+) cells with cartilage PG seemed to be critical for arthritis induction. Arthritis never developed after transfer of naive wild-type cells. The arthritis was characterized as a chronic progressive disease with intermittent spontaneous exacerbations and remissions. Inflamed joints showed extensive cartilage damage and bone erosions leading to massive ankylosis in peripheral joints. These PG epitope-specific TCR-5/4E8-Tg mice can be valuable research tools for studying antigen-driven T cell regulation in arthritis, and migration of T cells to the joints. In addition the model may be used for the development of immune modulating strategies in T cell-mediated autoimmune diseases.
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