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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

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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Autores principales: Sobek, Vera, Birkner, Nico, Falk, Ingrid, Würch, Andreas, Kirschning, Carsten J, Wagner, Hermann, Wallich, Reinhard, Lamers, Marinus C, Simon, Markus M
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC546283/
https://www.ncbi.nlm.nih.gov/pubmed/15380043
http://dx.doi.org/10.1186/ar1212
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author Sobek, Vera
Birkner, Nico
Falk, Ingrid
Würch, Andreas
Kirschning, Carsten J
Wagner, Hermann
Wallich, Reinhard
Lamers, Marinus C
Simon, Markus M
author_facet Sobek, Vera
Birkner, Nico
Falk, Ingrid
Würch, Andreas
Kirschning, Carsten J
Wagner, Hermann
Wallich, Reinhard
Lamers, Marinus C
Simon, Markus M
author_sort Sobek, Vera
collection PubMed
description 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)-γ 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-γ 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.
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spelling pubmed-5462832005-02-01 Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease Sobek, Vera Birkner, Nico Falk, Ingrid Würch, Andreas Kirschning, Carsten J Wagner, Hermann Wallich, Reinhard Lamers, Marinus C Simon, Markus M Arthritis Res Ther Research Article 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)-γ 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-γ 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. BioMed Central 2004 2004-07-19 /pmc/articles/PMC546283/ /pubmed/15380043 http://dx.doi.org/10.1186/ar1212 Text en Copyright © 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 article's original URL.
spellingShingle Research Article
Sobek, Vera
Birkner, Nico
Falk, Ingrid
Würch, Andreas
Kirschning, Carsten J
Wagner, Hermann
Wallich, Reinhard
Lamers, Marinus C
Simon, Markus M
Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease
title Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease
title_full Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease
title_fullStr Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease
title_full_unstemmed Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease
title_short Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease
title_sort direct toll-like receptor 2 mediated co-stimulation of t cells in the mouse system as a basis for chronic inflammatory joint disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC546283/
https://www.ncbi.nlm.nih.gov/pubmed/15380043
http://dx.doi.org/10.1186/ar1212
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