Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis.
Adjuvant arthritis (AA) can be induced in Lewis rats by immunization with mycobacterial antigens. Passive transfer of a T cell clone recognizing the 180-188 amino acid sequence in mycobacterial heat shock protein 60 (hsp60) was found to induce AA. In the present study, we investigated whether tolerance was obtained for this AA-associated T cell epitope after intranasal or s.c. administration of a peptide containing this epitope. Two 15-mer peptides containing the mycobacterial hsp60 sequences 176-190 and 211-225 were used; 176-190 contained the T cell epitope 180-188, which was recognized by the arthritogenic T cell clone A2b and was the immunodominant hsp60 T cell epitope after induction of AA, and 211-225 contained a T cell epitope that was recognized both after induction of arthritis with whole Mycobacterium tuberculosis and after immunization with mycobacterial hsp60. In rats treated intranasally or subcutaneously with 176-190 and immunized with mycobacterial hsp60, proliferative responses to 176-190 were reduced. Proliferative responses to 211-225 and to whole mycobacterial hsp60 were not affected. AA was inhibited intranasally in the 176-190-treated rats but not in the 211-225-treated rats. Moreover, intranasal 176-190 led to similar arthritis-protective effects in a nonmicrobially induced experimental arthritis (avridine-induced arthritis). Therefore, tolerance for a disease-triggering, microbial cartilage-mimicking epitope may cause resistance to arthritis irrespective of the actual trigger leading to development of the disease.
Prakken
B J
BJ
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht, The Netherlands. bprakken@wkz.ruu.nl
van der Zee
R
R
Anderton
S M
SM
van Kooten
P J
PJ
Kuis
W
W
van Eden
W
W
D000281:Administration, Intranasal; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D018834:Chaperonin 60 / Q000737:chemistry*; D003959:Diamines / Q000633:toxicity; D000939:Epitopes / Q000008:administration & dosage / Q000627:therapeutic use*; D007111:Immunity, Cellular; D007279:Injections, Subcutaneous; D008297:Male; D009161:Mycobacterium / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D018834:Chaperonin 60; D003959:Diamines; D000939:Epitopes; C006270:avridine