Differential activities of immunogenic collagen type II peptides in the induction of nasal tolerance to collagen-induced arthritis

Nasal tolerance has recently been used to modulate immune responses in anim al models of autoimmunity. We have compared immunogenic collagen type II (C II) peptides for induction of nasal tolerance in DBA/1 mice to collagen-ind uced arthritis (CIA). Three synthetic peptides corresponding to T cell-stim ulating sequences of alpha 1(II)-CB11, 260-270, 245-270 and 259-273, one pe ptide analog 245-270 (A(260)B(261)N(263)) and one myelin basic protein (MBP ) peptide 89-101 were administered intranasally to DBA/1 mice respectively (total 300 mu g peptide/mouse on three consecutive days) 10 days prior to C II immunization. Forty percent of CII245-270 (P<0.05) and 20% CII260-270 (P >0.05) treated mice did not develop arthritis whilst all of the mice treate d with CII245-270 (A(260)B(261)N(263)) or CII259-273 developed arthritis co mpared to those in control groups (PBS- and MBP89-101-treated). The mice in either the CII245-270- or CII260-270-treated group which developed arthrit is had a significantly delayed onset and their disease was less severe both clinically and histologically. All mice in both CII245-270- and CII260-270 -treated groups had a reduced serum level of anti-CII antibody (P<0.01), wi th a marked reduction of IgG(2a). Drain lymph node (LN) cells taken 7 days after CII immunization from these mice showed a significant reduction of in terferon (IFN)-gamma (P<0.01) production upon in vitro stimulation with CII . These results indicate that intranasal administration of synthetic CII pe ptides can control CIA, which is achieved by down-regulating the Th1 CII-in duced responses. In addition, they stress that a fine 'tuning' of the pepti de able to induce 'tolerance' is required to achieve the optimal effect. (C ) 1999 Academic Press.