title: Streptococcus sanguis modulates type II collagen-induced arthritis in DBA/1J mice.
abstract: Native type II collagen is tolerogenic when given orally or i.p. to DBA/1J mice and induces autoimmune arthritis when given s.c. in CFA. The tolerogenic epitope is contained in cyanogen bromide fragment 11 (CB11) and is structurally mimicked by PGEQGPK within the platelet aggregation-associated protein (PAAP) on Streptococcus sanguis. To learn whether S. sanguis modulates transmucosally the Ag-specific development of autoimmune arthritis, DBA/1J pups were given live S. sanguis, CB11, or type II collagen intragastrically. Feeding S. sanguis at 6 days postpartum delayed the onset of arthritis, and reduced the rate, final severity, and percentage of affected limbs. Next, PAAP(+) S. sanguis and type II collagen were tested for T cell cross-reactivity. T cells primed with the tolerogenic epitope of type II collagen proliferated more when incubated with PAAP(+) S. sanguis than with PAAP(-) Streptococcus gordonii or type II collagen, suggesting an Ag-specific transmucosal tolerogenic effect. In neonatal mice, therefore, bacterial surface Ags that mimic self can transmucosally stimulate Ag-specific inhibitory T cells. In adult mice immunized with type II collagen, these Ag-specific inhibitory T cells manifest later as attenuated arthritis. The PAAP(+) S. sanguis appear to activate adult memory, rather than naive, type II collagen-specific T cells, suggesting that systemic challenge with commensal self-mimicking microorganisms may perpetuate existing autoimmunity, but not initiate autorecognition.
authors.affiliation: Department of Preventive Sciences and Minnesota Oral Health Clinical Research Center, University of Minnesota, Minneapolis, MN 55455, USA. costa002@umn.edu
authors.forename: Massimo
authors.initials: M
authors.lastname: Costalonga
authors.forename: James S
authors.initials: JS
authors.lastname: Hodges
authors.forename: Mark C
authors.initials: MC
authors.lastname: Herzberg
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D015551:Autoimmunity; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D024043:Collagen Type II / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D017634:Self Tolerance; D013290:Streptococcal Infections / Q000150:complications / Q000276:immunology; D013298:Streptococcus sanguis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D024043:Collagen Type II; D000939:Epitopes; C111210:platelet aggregation-associated protein, Streptococcus