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 animal models of autoimmunity. We have compared immunogenic collagen type II (CII) peptides for induction of nasal tolerance in DBA/1 mice to collagen- induced arthritis (CIA). Three synthetic peptides corresponding to T cell- stimulating sequences of α1(II)-CB11, 260-270, 245-270 and 259-273, one peptide analog 245-270 (A²⁶⁰B²⁶¹N²⁶³) and one myelin basic protein (MBP) peptide 89-101 were administered intranasally to DBA/1 mice respectively (total 300 μg peptide/mouse on three consecutive days) 10 days prior to CII 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 treated with CII₂₄₅-₂₇₀ (A²⁶⁰B²⁶¹N²⁶³) or CII₂₅₉-₂₇₃ developed arthritis compared to those in control groups (PBS- and MBP₈₉-₁₀₁-treated). The mice in either the CII₂₄₅-₂₇₀or CII₂₆₀-₂₇₀-treated group which developed arthritis 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), with a marked reduction of IgG(za). Drain lymph node (LN) cells taken 7 days after CII immunization from these mice showed a significant reduction of interferon (IFN)-?? (P<0.01) production upon in vitro stimulation with CII. These results indicate that intranasal administration of synthetic CII peptides can control CIA, which is achieved by down-regulating the Th1 CII-induced responses. In addition, they stress that a fine 'tuning' of the peptide able to induce 'tolerance' is required to achieve the optimal effect.