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HSP Reactive T Cells are Anti-Inflammatory and Disease Suppressive in Arthritic Diseases

  • Femke Broere
  • Suzanne E. Berlo
  • Teun Guichelaar
  • Lotte Wieten
  • Ruurd Van Der Zee
  • Willem Van EdenEmail author
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 5)

Abstract:

Immune responses to certain heat-shock proteins (HSP) develop in virtually all inflammatory diseases; however, the significance of such responses is only now becoming clear. In models of experimental arthritis, HSPs can prevent or arrest inflammatory damage, and in initial clinical trials in patients with chronic inflammatory diseases, including rheumatoid arthritis, HSP peptides have been shown to promote the production of anti-inflammatory cytokines, indicating immunoregulatory potential of HSP. Heat shock proteins, also called stress-proteins, are ubiquitous self-antigens that are over-expressed in inflamed tissues. For some reason, the prokaryotic homologous proteins, present in every bacterial species, are dominantly immunogenic. This is striking, especially given the fact that these proteins have large areas of sequence homologies with the host (mammalian) counterparts. Furthermore, in experimental models of arthritis, immunisation with bacterial heat shock proteins has been seen to lead to inhibition of disease development. In addition oral or nasal administration has similarly been seen to lead to disease inhibition. Based on the experimental evidence collected, it becomes attractive to suppose that the exposure to homologues of these self antigens, as present in for instance the bacterial intestinal flora, has a decisive impact on the regulation of self tolerance at the level of T cells. If so, it becomes attractive to use such proteins or their derivative peptides for modulation of inflammation relevant T cells as an antigen specific immunotherapy approach, without the immediate necessity of defining disease specific auto-antigens

Keywords:

Heat shock proteins arthritis T cells immune regulation 

Abbreviations

APC

antigen presenting cells

APL

altered peptide ligands

BCG

Bacillus Calmette-Guérin

DC

dendritic cells

DMARDs

disease-modifying anti-rheumatic drugs

EAE

experimental autoimmune encephalomyelitis

HSP

heat shock proteins

IBD

inflammatory bowel disease

IL-10

interleukin-10

MHC

major histocompatibility complex

RA

Rheumatoid arthritis

TCR

T cell receptor

Tg

transgenic

TGF-β

transforming growth factor-β

TLR

toll like receptor

TNFα

tumor necrosis factor-alpha

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Femke Broere
    • 1
  • Suzanne E. Berlo
    • 1
  • Teun Guichelaar
    • 1
  • Lotte Wieten
    • 1
  • Ruurd Van Der Zee
    • 1
  • Willem Van Eden
    • 2
    Email author
  1. 1.Division of Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary MedicineUniversity of UtrechtUtrechtThe Netherlands
  2. 2.Division of Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary MedicineUniversity of UtrechtUtrechtThe Netherlands

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