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

被引:26
作者
Berlo, SE
van Kooten, PJ
ten Brink, CB
Hauet-Broere, F
Oosterwegel, MA
Glant, TT
Van Eden, W
Broeren, CP
机构
[1] Univ Utrecht, Fac Med Vet, Div Immunol, Dept Infect Dis & Immunol, NL-3584 CL Utrecht, Netherlands
[2] Univ Utrecht, Dept Immunol, Ctr Med, Wilhelmia Childrens Hosp, NL-3584 EA Utrecht, Netherlands
[3] Rush Univ, Med Ctr, Sect Mol Med, Dept Orthoped Surg, Chicago, IL 60612 USA
基金
美国国家卫生研究院;
关键词
arthritis; proteoglycan; rheumatoid arthritis; T cell receptor; transgenic mouse;
D O I
10.1016/j.jaut.2005.09.017
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 V alpha 1.1 and V beta 4 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.RAG(2-/-) mice. In vivo activation of TCR5/4E8-Tg CD4(+)V beta 4(+) 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. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:172 / 180
页数:9
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