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

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-i...

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Hauptverfasser: Sobek, Vera (VerfasserIn) , Birkner, Nico (VerfasserIn) , Falk, Ingrid (VerfasserIn) , Würch, Andreas (VerfasserIn) , Kirschning, Carsten J. (VerfasserIn) , Wagner, Hermann (VerfasserIn) , Wallich, Reinhard (VerfasserIn) , Lamers, Marinus C. (VerfasserIn) , Simon, Markus M. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2004
In: Arthritis Research & Therapy
Year: 2004, Jahrgang: 6, Heft: 5, Pages: R433-446
ISSN:1465-9913
DOI:10.1186/ar1212
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1186/ar1212
Verlag, lizenzpflichtig, Volltext: https://arthritis-research.biomedcentral.com/articles/10.1186/ar1212
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Verfasserangaben:Vera Sobek, Nico Birkner, Ingrid Falk, Andreas Würch, Carsten J. Kirschning, Hermann Wagner, Reinhard Wallich, Marinus C. Lamers, and Markus M. Simon

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520 |a 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 the etiological agent of Lyme disease, namely Borrelia burgdorferi, but not its delipidated form or lipopolysaccharide, was able to provide direct antigen-nonspecific co-stimulatory signals to both antigen-sensitized naive T cells and cytotoxic T lymphocyte (CTL) lines via TLR-2. Lip-OspA induced the proliferation and interferon (IFN)-gamma secretion of purified, anti-CD3-sensitized, naive T cells from C57BL/6 mice but not from TLR-2-deficient mice. Induction of proliferation and IFN-gamma secretion of CTL lines by Lip-OspA was independent of T cell receptor (TCR) engagement but was considerably enhanced after suboptimal TCR activation and was inhibitable by monoclonal antibodies against TLR-2. 
650 4 |a Animals 
650 4 |a Antigens, Surface 
650 4 |a Arthritis, Rheumatoid 
650 4 |a Bacterial Outer Membrane Proteins 
650 4 |a Bacterial Vaccines 
650 4 |a CD8-Positive T-Lymphocytes 
650 4 |a Cell Line 
650 4 |a Cell Proliferation 
650 4 |a Female 
650 4 |a Inflammation 
650 4 |a Interferon-gamma 
650 4 |a Lipoproteins 
650 4 |a Lymphocyte Activation 
650 4 |a Lymphocyte Culture Test, Mixed 
650 4 |a Male 
650 4 |a Membrane Glycoproteins 
650 4 |a Mice 
650 4 |a Mice, Inbred C57BL 
650 4 |a Mice, Inbred Strains 
650 4 |a Receptors, Cell Surface 
650 4 |a Recombinant Proteins 
650 4 |a T-Lymphocyte Subsets 
650 4 |a T-Lymphocytes 
650 4 |a T-Lymphocytes, Cytotoxic 
650 4 |a Toll-Like Receptor 2 
650 4 |a Toll-Like Receptors 
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700 1 |a Lamers, Marinus C.  |e VerfasserIn  |4 aut 
700 1 |a Simon, Markus M.  |e VerfasserIn  |4 aut 
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