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Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease.doc

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Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease

Available online /content/6/5/R433 Research article Open Access Vol 6 No 5 Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease Vera Sobek1, Nico Birkner2, Ingrid Falk1, Andreas Würch1, Carsten J Kirschning3, Hermann Wagner3, Reinhard Wallich4, Marinus C Lamers2 and Markus M Simon1 1Department of Cellular Immunology, Max-Planck-Institut für Immunbiologie, Freiburg, Germany 2Department of Developmental Immunology, Max-Planck-Institut für Immunbiologie, Freiburg, Germany 3Technische Universit?t München, Klinikum rechts der Isar, München, Germany 4Universit?tsklinikum Heidelberg, Institut für Immunologie, Heidelberg, Germany Corresponding author: Markus M Simon, simon@immunbio.mpg.de Received: 5 Mar 2004 Revisions requested: 5 Apr 2004 Revisions received: 18 May 2004 Accepted: 18 Jun 2004 Published: 19 Jul 2004 Arthritis Res Ther 2004, 6:R433-R446 (DOI 10.1186/ar1212) /content/6/5/R433 ? 2004 Sobek et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the articles original URL. Abstract The pathogenesis of chronic inflammatory joint diseases such as adult and juvenile rheumatoid arthritis and Lyme arthritis is still poorly understood. Central to the various hypotheses in this respect is the notable involvement of T and B cells. Here we develop the premise that the nominal antigen-independent, polyclonal activation of preactivated T cells via Toll-like receptor (TLR)-2 has a pivotal role in the initiation and perpetuation of pathogen-induced chronic inflammatory joint disease. We support this with the following evidence. Both naive and effector T cells express TLR-2. A prototypic lipoprotein, Lip-OspA, from burgdorferi, but not its delipidated form or lipopolysaccharide, was able to provide