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.