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

• Published in: Proceedings of the National Academy of Sciences - PNAS 1997-04, Vol.94 (7), p.3284-3289
• Main Authors: Prakken, Berent J., Van Der Zee, Ruurd, Anderton, Stephen M., Peter J. S. Van Kooten, Kuis, Wietse, Van Eden, Willem
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Amino acids; Animals; Antigens; Arthritis; Arthritis, Experimental - immunology; Arthritis, Experimental - therapy; Autoimmune diseases; Bacteria; Biological Sciences; Chaperonin 60 - chemistry; Diamines - toxicity; Epitopes; Epitopes - administration & dosage; Epitopes - therapeutic use; Exercise tolerance; Immune tolerance; Immunity (Disease); Immunity, Cellular; Immunization; Injections, Subcutaneous; Lymph nodes; Male; Mycobacterium - immunology; Mycobacterium tuberculosis; Peptides; Proteins; Rats; Rats, Inbred Lew; Rodents; T lymphocytes; T-Lymphocytes - immunology; Transplantation tolerance
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.7.3284

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.