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Infection and Immunity, June 2001, p. 4072-4078, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.4072-4078.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Induction of Autoimmune Valvular Heart Disease by Recombinant Streptococcal M Protein

Anthony Quinn,1,dagger Stanley Kosanke,2 Vincent A. Fischetti,3 Stephen M. Factor,4 and Madeleine W. Cunningham1,*

Departments of Microbiology and Immunology1 and Department of Pathology,2 University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, and Laboratory of Bacterial Pathogenesis, Rockefeller University, New York,3 and Department of Pathology, Albert Einstein College of Medicine and Jacobi Medical Center, Bronx,4 New York

Received 9 November 2000/Returned for modification 10 January 2001/Accepted 19 March 2001

Rheumatic heart disease is an autoimmune sequela of group A streptococcal infection. Previous studies have established that streptococcal M protein is structurally and immunologically similar to cardiac myosin, a well-known mediator of inflammatory heart disease. In this study, we investigated the hypothesis that streptococcal M protein could produce inflammatory valvular heart lesions similar to those seen in rheumatic fever (RF). Fifty percent (3 of 6) of Lewis rats immunized with recombinant type 6 streptococcal M protein (rM6) developed valvulitis as well as focal lesions of myocarditis. Valvular lesions initiated at the valve surface endothelium spread into the valve. Anitschkow cells and verruca-like lesions were present. T cells from rM6-immunized rats proliferated in the presence of purified cardiac myosin, but not skeletal myosin. A T-cell line produced from rM6-treated rats proliferated in the presence of cardiac myosin and rM6 protein. The study demonstrates that the Lewis rat is a model of valvular heart disease and that streptococcal M protein can induce an autoimmune cell-mediated immune attack on the heart valve in an animal model. The data support the hypothesis that a bacterial antigen can break immune tolerance in vivo, an important concept in autoimmunity.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Biomedical Research Center, 975 N.E. 10th St., Oklahoma City, OK 73104. Phone: (405) 271-3128. Fax: (405) 271-2217. E-mail: madeleine-cunningham{at}ouhsc.edu.

dagger Present address: Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121.

Infection and Immunity, June 2001, p. 4072-4078, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.4072-4078.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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