Oral Administration of Collagen Conjugated with Cholera Toxin Induces Tolerance to Type II Collagen and Suppresses Chondritis in an Animal Model of Autoimmune Ear Disease

Abstract

B10.RIII (H-2^r) mice were orally administered cyanogen bromide peptide 11 (CB 11) or cholera toxin B (CTB)–conjugated CB 11 to induce tolerance in collagen-induced autoimmune ear disease. Oral administration of a high dosage of CB 11 provided partial protection from chondritis. However, administration of a tiny amount of CTB-CB 11 conjugate effectively suppressed chondritis. Oral administration of CTB-CB 11 conjugate did not alter the stimulation of T cells in vitro or the fine specificities of B cells. The oral administration of CTB-CB 11 caused a higher level of type II collagen-specific IgG and its subclass. Interestingly, increases of Th1 cytokine (interferon-γ) in Peyer's patches and of Th1/Th2 cytokines (interleukin-2 and interleukin-4) in lymph nodes were detected in mice that had been fed CTB-CB 11. An increase of CD8⁺ T cells in the Peyer's patches with a decrease of CD8⁺ T cells in lymph nodes was seen in mice that had been fed CTB-CB 11. These results suggest that protection from chondritis by oral administration of minute amounts of CTB-CB 11 conjugate can be achieved by a mechanism distinct from that of conventional oral tolerance induction.