| JWissmille 2004-10-24, 2:08 am |
| http://www.ncbi.nlm.nih.gov/entrez/...db=pubmed&dopt=
Abstract&list_uids=15380043
Arthritis Res Ther. 2004;6(5):R433-46. Epub 2004 Jul 19.
*Direct Toll-like receptor 2 mediated co-stimulation of T cells in the
mouse system as a basis for chronic inflammatory joint disease.*
*Sobek V, Birkner N, Falk I, Wurch A, Kirschning CJ, Wagner H, Wallich
R, Lamers MC, Simon MM.*
Department of Cellular Immunology, Max-Planck-Institut fur
Immunbiologie, Freiburg, Germany. simon@immunbio.mpg.de
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.
PMID: 15380043 [PubMed - in process]
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