Naive transgenic T cells expressing cartilage proteoglycan-specific TCR induce arthritis upon in vivo activation.
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.
Berlo
Suzanne E
SE
Department of Infectious Diseases and Immunology, Division of Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, The Netherlands.
van Kooten
Peter J
PJ
Ten Brink
Corlinda B
CB
Hauet-Broere
Femke
F
Oosterwegel
Mariëtte A
MA
Glant
Tibor T
TT
Van Eden
W
W
Broeren
Chris P
CP
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology*; D002358:Cartilage, Articular / Q000276:immunology* / Q000378:metabolism; D003001:Cloning, Molecular; D018014:Gene Transfer Techniques; D006801:Humans; D006825:Hybridomas; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D011509:Proteoglycans; D016693:Receptors, Antigen, T-Cell, alpha-beta