title: Induction of autoimmune valvulitis in Lewis rats following immunization with peptides from the conserved region of group A streptococcal M protein.
abstract: Rheumatic heart disease (RHD) is considered to be an autoimmune disorder mediated by group A streptococcal (GAS) M protein-specific T cells and antibodies that cross-react with cardiac antigens and epitopes of the GAS M protein. In this study, Lewis rats were immunized with a pool of overlapping peptides spanning the conserved region of the GAS M protein in Complete Freund's Adjuvant, followed by immunization with Bordetella pertussis. Controls received adjuvants alone. Spleen-derived lymphocytes from rats immunized with the conserved region peptides proliferated in response to the immunogen and to cardiac myosin. Moreover, histological examination of cardiac tissue from rats immunized with conserved region peptides revealed the presence of inflammatory lesions in both the myocardium and valve tissue indicating a role for GAS M protein-specific autoreactive T cells in the development of cardiac lesions. This study may support the use of the rat model of autoimmune valvulitis to investigate the immunopathogenesis of RHD and possible preventive strategies.
authors.affiliation: Microbiology and Immunology, School of Biomedical Sciences, James Cook University, Townsville, Australia.
authors.forename: Robyn S
authors.initials: RS
authors.lastname: Lymbury
authors.forename: Colleen
authors.initials: C
authors.lastname: Olive
authors.forename: Kellie A
authors.initials: KA
authors.lastname: Powell
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hirst
authors.forename: Justin T
authors.initials: JT
authors.lastname: LaBrooy
authors.forename: Natkunam
authors.initials: N
authors.lastname: Ketheesan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D017124:Conserved Sequence; D005260:Female; D006349:Heart Valve Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D012214:Rheumatic Heart Disease / Q000209:etiology / Q000276:immunology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D010446:Peptide Fragments; C014689:streptococcal M protein