B- and T-cell responses in group a streptococcus M-protein- or Peptide-induced experimental carditis.
The etiology of rheumatic fever and rheumatic heart disease (RF/RHD) is believed to be autoimmune, involving immune responses initiated between streptococcal and host tissue proteins through a molecular mimicry mechanism(s). We sought to investigate the humoral and cellular responses elicited in a Lewis rat model of group A streptococcus M-protein- or peptide-induced experimental valvulitis/carditis, a recently developed animal model which may, in part, represent human rheumatic carditis. Recombinant streptococcal M5 protein elicited opsonic antibodies in Lewis rats, and anti-M5 antisera recognized epitopes within the B- and C-repeat regions of M5. One peptide from the streptococcal M5 protein B-repeat region (M5-B.6, amino acids 161 to 180) induced lymphocytes that responded to both recombinant M5 and cardiac myosin. Rats immunized with streptococcal M5 protein developed valvular lesions, distinguished by infiltration of CD3(+), CD4(+), and CD68(+) cells into valve tissue, consistent with human studies that suggest that RF/RHD are mediated by inflammatory CD4(+) T cells and CD68(+) macrophages. The current study provides additional information that supports the use of the rat autoimmune valvulitis model for investigating RF/RHD.
Gorton
Davina
D
Microbiology and Immunology, School of Veterinary and Biomedical Sciences, James Cook University, Solander Drive, Douglas 4811, Australia. davina.gorton@jcu.edu.au
Govan
Brenda
B
Olive
Colleen
C
Ketheesan
Natkunam
N
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology* / Q000302:isolation & purification; D001402:B-Lymphocytes / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000302:isolation & purification; D002352:Carrier Proteins / Q000276:immunology* / Q000302:isolation & purification; D004696:Endocarditis / Q000139:chemically induced* / Q000276:immunology*; D005260:Female; D006351:Heart Valves / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D009206:Myocardium / Q000473:pathology; D009218:Myosins / Q000276:immunology; D051381:Rats; D013297:Streptococcus pyogenes / Q000737:chemistry*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C014689:streptococcal M protein; D009218:Myosins