Heat shock protein 60 and adjuvant arthritis: a model for T cell regulation in human arthritis.
Heat shock proteins (hsp) are highly conserved, immune-dominant microbial proteins, whose expression is increased at sites of inflammation. In the experimental model of adjuvant arthritis (AA) immune responses to hsp determine the outcome of disease. AA can be transferred with a single T cell clone specific for a sequence of mycobacterial hsp65 (Mhsp65). Immunization with whole Mhsp65 on the other hand, protects in virtually all forms of experimental arthritis, including AA. This protective effect seems the consequence of the induction of a T cell response directed against self-hsp60. A similar protective effect of self-hsp60-specific T cells seems present in patients with a spontaneous remitting form of juvenile idiopathic arthritis. Next to hsp60, other hsp have similar protective effects in arthritis, while other conserved microbial proteins lack such capacity. Nasal administration of hsp60 peptides induces IL-10-driven regulatory T cells that are highly effective in suppressing arthritis. Thus hsp60, or peptides derived from hsp60, are suitable candidates for immune therapy in chronic arthritis.
Prakken
Berent J
BJ
Department of Paediatric Immunology, University Medical Centre Utrecht, Wilhelmina Children's Hospital, Home Mailbox KC.03.063.0, PO Box 85090, 3508 AB, Utrecht, The Netherlands.
Roord
Sarah
S
Ronaghy
Arash
A
Wauben
Marca
M
Albani
Salvatore
S
van Eden
Willem
W
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000628:therapy; D001171:Arthritis, Juvenile / Q000276:immunology* / Q000628:therapy; D001426:Bacterial Proteins / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology*; D018833:Chaperonins / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D010446:Peptide Fragments; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins