Nasal administration of arthritis-related T cell epitopes of heat shock protein 60 as a promising way for immunotherapy in chronic arthritis.
Adjuvant Arthritis (AA) can be induced in Lewis rats by immunisation with mycobacterial antigens. The disease can be passively transferred with T cell clone A2b, which recognises the 180-188 amino acid sequence in mycobacterial heat shock protein 60 (hsp60) and which crossreacts with crude cartilage proteoglycans. We succeeded to induce peripheral tolerance to this AA-associated T cell epitope following nasal administration of a peptide containing this epitope (mycobacterial hsp60 176-190). In rats treated nasally with 176-190 and immunised with mycobacterial hsp60, proliferative responses to 176-190 were reduced. AA was inhibited nasally with 176-190 treated rats and not in rats nasally treated with a control mycobacterial hsp60 peptide (211-225). Moreover, nasal 176-190 led to similar arthritis protective effects in a non-microbially induced experimental arthritis (avridine induced arthritis). In a subsequent study we tried to prevent and to treat AA through nasal administration of mycobacterial hsp60 peptide 180-188 and a peptide analogue of 180-188, 180-188(L183->A) (Alanine 183), which has been shown to have an increased MHC-binding affinity for rat RT1 Bl and an increased capacity to inhibit the proliferative A2b response in vitro. We found that nasal administration of 180-188 had a moderate arthritis suppressive effect in AA, whereas its analogue peptide Alanine 183, had a strong suppressive effect. This strong arthritis suppressive effect was only partly due to the higher MHC-binding affinity for rat RT1 Bl. Furthermore, it was possible to passively transfer nasal Alanine 183 induced disease protection. The present findings may in our view offer novel prospects for immunotherapy through nasal administration of (analogue) peptides, with a mimicry relationship with joint specific cartilage proteoglycan epitopes.
Prakken
B
B
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht, The Netherlands. bprakken@ucsd.edu
Wauben
M
M
van Kooten
P
P
Anderton
S
S
van der Zee
R
R
Kuis
W
W
van Eden
W
W
D000281:Administration, Intranasal; D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000628:therapy; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D018834:Chaperonin 60 / Q000008:administration & dosage* / Q000276:immunology*; D000939:Epitopes / Q000008:administration & dosage; D006801:Humans; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007167:Immunotherapy / Q000379:methods*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology
D018834:Chaperonin 60; D000939:Epitopes