Stimulation of suppressive T cell responses by human but not bacterial 60-kD heat-shock protein in synovial fluid of patients with rheumatoid arthritis

J Clin Invest. 1997 Jul 15;100(2):459-63. doi: 10.1172/JCI119553.


In several animal models of rheumatoid arthritis (RA), T cell responses to self 60-kD heat-shock protein 60 (hsp60) protect against the induction of arthritis. The nature of this suppressive T cell activity induced by self hsp60 is not clear. In the present study, T cell responses to human (self) hsp60 in RA in terms of type 1 (T1) and type 2 (T2) T cell activity were assessed. The results show that human and not bacterial hsp60-reactive synovial fluid (SF) T cells of patients with RA proliferate in the presence of the T2 cell growth factor IL-4. SF T cells stimulated with human hsp60 produced significantly lower amounts of IFN-gamma and higher amounts of IL-4 than SF T cells stimulated with bacterial hsp60 (P </= 0.002 and 0.05, respectively), and consequently a lower T1/T2 cell cytokine ratio was observed for human versus bacterial hsp60 (P </= 0.004). Additionally, human and not mycobacterial hsp60-specific T cell lines suppressed TNF-alpha production. Together, our results suggest that human hsp60, as overexpressed in inflamed synovium of patients with RA, can contribute to suppression of arthritis by the stimulation of regulatory suppressive T cell activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies / immunology
  • Arthritis, Rheumatoid / immunology*
  • Bacterial Proteins / immunology*
  • Cell Line
  • Chaperonin 60 / immunology*
  • Female
  • Humans
  • Immune Tolerance
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Synovial Fluid / chemistry*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Antibodies
  • Bacterial Proteins
  • Chaperonin 60
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma