Stimulation of suppressive T cell responses by human but not bacterial 60-kD heat-shock protein in synovial fluid of patients with rheumatoid arthritis.
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.
van Roon
J A
JA
Department of Rheumatology & Clinical Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands.
van Eden
W
W
van Roy
J L
JL
Lafeber
F J
FJ
Bijlsma
J W
JW
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002460:Cell Line; D018834:Chaperonin 60 / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000906:Antibodies; D001426:Bacterial Proteins; D018834:Chaperonin 60; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma