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.
B10.RIII (H-2r) mice were orally administered cyanogen bromide peptide 11 (CB11) or cholera toxin B (CTB)-conjugated CB11 to induce tolerance in collagen-induced autoimmune ear disease. Oral administration of a high dosage of CB11 provided partial protection from chondritis. However, administration of a tiny amount of CTB-CB11 conjugate effectively suppressed chondritis. Oral administration of CTB-CB11 conjugate did not alter the stimulation of T cells in vitro or the fine specificities of B cells. The oral administration of CTB-CB11 caused a higher level of type II collagen-specific IgG and its subclass. Interestingly, increases of TH1 cytokine (interferon-gamma) 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-CB11. 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-CB11. These results suggest that protection from chondritis by oral administration of minute amounts of CTB-CB11 conjugate can be achieved by a mechanism distinct from that of conventional oral tolerance induction.
Kim
N
N
Department of Medicine, University of Tennessee, Memphis 38163, USA.
Cheng
K C
KC
Kwon
S S
SS
Mora
R
R
Barbieri
M
M
Yoo
T J
TJ
D000284:Administration, Oral; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D002772:Cholera Toxin / Q000494:pharmacology*; D003094:Collagen / Q000276:immunology*; D003488:Cyanogen Bromide / Q000494:pharmacology; D004427:Ear Diseases / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D010007:Osteochondritis / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000494:pharmacology
D010455:Peptides; D003094:Collagen; D002772:Cholera Toxin; D003488:Cyanogen Bromide