The spontaneous remission of juvenile idiopathic arthritis is characterized by CD30+ T cells directed to human heat-shock protein 60 capable of producing the regulatory cytokine interleukin-10.
OBJECTIVE
To test the hypothesis that T cell reactivity to self heat-shock protein 60 (Hsp60) in patients with remitting juvenile idiopathic arthritis (JIA) is part of an antiinflammatory, regulatory mechanism.


METHODS
Using peripheral blood-derived mononuclear cells (PBMCs) and synovial fluid-derived mononuclear cells (SFMCs) obtained from patients with JIA, we analyzed the expression of CD30 and the induction of regulatory cytokines in response to human and mycobacterial Hsp60.


RESULTS
In oligoarticular JIA patients, in vitro activation of PBMCs and SFMCs with Hsp60 induced a high expression of CD30 on CD4+, activated (HLA-DR-positive), memory (CD45RO+) T cells. The expression of CD30 induced by human Hsp60 was much higher than that induced by mycobacterial Hsp60. In oligoarticular JIA patients with active disease, the expression of CD30 in response to human Hsp60 was paralleled by a high interleukin-10 (IL-10):interferon-gamma (IFNgamma) ratio. In addition, restimulated human Hsp60-specific T cell lines from oligoarticular JIA patients showed a high production of IL-10 and a low production of IFNgamma. In contrast, PBMCs and SFMCs from polyarticular JIA patients responded to human Hsp60 with virtually no expression of CD30 and a low IL-10:IFNgamma ratio.


CONCLUSIONS
The results show that T cells responding to human Hsp60 in oligoarticular JIA patients express CD30, and during active phases of the disease, these T cells have a cytokine profile with a high IL-10:IFNgamma ratio. These findings suggest that in oligoarticular JIA patients, human Hsp60-specific CD4+ cells have a regulatory function and contribute to disease remission.
de Kleer
I M
IM
University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Kamphuis
S M
SM
Rijkers
G T
GT
Scholtens
L
L
Gordon
G
G
De Jager
W
W
Häfner
R
R
van de Zee
R
R
van Eden
W
W
Kuis
W
W
Prakken
B J
BJ
D001171:Arthritis, Juvenile / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D018834:Chaperonin 60 / Q000494:pharmacology*; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D017730:Ki-1 Antigen / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D009161:Mycobacterium; D012075:Remission, Spontaneous
D018834:Chaperonin 60; D016207:Cytokines; D017730:Ki-1 Antigen; D016753:Interleukin-10; D007371:Interferon-gamma