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

Arthritis Res Ther. 2004;6(5):R433-46. doi: 10.1186/ar1212. Epub 2004 Jul 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Bacterial Outer Membrane Proteins / immunology
  • Bacterial Vaccines
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Line
  • Cell Proliferation
  • Female
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interferon-gamma / metabolism
  • Lipoproteins / immunology
  • Lymphocyte Activation / physiology*
  • Lymphocyte Culture Test, Mixed / methods
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / physiology*
  • Recombinant Proteins / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / physiology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / physiology
  • Toll-Like Receptor 2
  • Toll-Like Receptors


  • Antigens, Surface
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Lipoproteins
  • Membrane Glycoproteins
  • OspA protein
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Interferon-gamma