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Infection and Immunity, May 2009, p. 2177-2183, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01514-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

B- and T-Cell Responses in Group A Streptococcus M-Protein- or Peptide-Induced Experimental Carditis{triangledown}

Davina Gorton,1* Brenda Govan,1 Colleen Olive,2 and Natkunam Ketheesan1

School of Veterinary and Biomedical Sciences, James Cook University, Townsville 4811, Australia,1 Queensland Institute of Medical Research, Herston 4006, Australia2

Received 15 December 2008/ Returned for modification 21 January 2009/ Accepted 26 February 2009

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.


* Corresponding author. Mailing address: Microbiology and Immunology, School of Veterinary and Biomedical Sciences, James Cook University, Solander Drive, Douglas 4811, Australia. Phone: 617 4781 6647. Fax: 617 4779 1526. E-mail: davina.gorton{at}jcu.edu.au

{triangledown} Published ahead of print on 9 March 2009.

Editor: J. N. Weiser


Infection and Immunity, May 2009, p. 2177-2183, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01514-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.