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Infection and Immunity, September 2001, p. 5345-5351, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5345-5351.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

T-Cell Reactivity against Streptococcal Antigens in the Periphery Mirrors Reactivity of Heart-Infiltrating T Lymphocytes in Rheumatic Heart Disease Patients

Luiza Guilherme,1,* Sandra E. Oshiro,1 Kellen C. Faé,1 Edécio Cunha-Neto,1 Guilherme Renesto,1 Anna C. Goldberg,1 Ana C. Tanaka,1 Pablo M. A Pomerantzeff,1 Maria H. Kiss,2 Clóvis Silva,2 Fanny Guzman,3 Manuel E. Patarroyo,3 Scott Southwood,4 Alessandro Sette,4 and Jorge Kalil1,5

Heart Institute, InCor,1 Children's Institute,2 and Clinical Immunology and Allergy, Department of Clinical Medicine,5 School of Medicine, University of São Paulo, São Paulo, Brazil; Instituto de Inmunologia, HSJD, Universidad Nacional de Colômbia, Bogotá, Colombia3; and Epimmune Inc., San Diego, California4

Received 30 January 2001/Returned for modification 17 April 2001/Accepted 6 June 2001

T-cell molecular mimicry between streptococcal and heart proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). We searched for immunodominant T-cell M5 epitopes among RHD patients with defined clinical outcomes and compared the T-cell reactivities of peripheral blood and intralesional T cells from patients with severe RHD. The role of HLA class II molecules in the presentation of M5 peptides was also evaluated. We studied the T-cell reactivity against M5 peptides and heart proteins on peripheral blood mononuclear cells (PBMC) from 74 RHD patients grouped according to the severity of disease, along with intralesional and peripheral T-cell clones from RHD patients. Peptides encompassing residues 1 to 25, 81 to 103, 125 to 139, and 163 to 177 were more frequently recognized by PBMC from RHD patients than by those from controls. The M5 peptide encompassing residues 81 to 96 [M5(81-96) peptide] was most frequently recognized by PBMC from HLA-DR7+ DR53+ patients with severe RHD, and 46.9% (15 of 32) and 43% (3 of 7) of heart-infiltrating and PBMC-derived peptide-reactive T-cell clones, respectively, recognized the M5(81-103) region. Heart proteins were recognized more frequently by PBMC from patients with severe RHD than by those from patients with mild RHD. The similar pattern of T-cell reactivity found with both peripheral blood and heart-infiltrating T cells is consistent with the migration of M-protein-sensitized T cells to the heart tissue. Conversely, the presence of heart-reactive T cells in the PBMC of patients with severe RHD also suggests a spillover of sensitized T cells from the heart lesion.

* Corresponding author. Mailing address: Laboratório Imunologia, Instituto do Coração-HC-FMUSP, Av. Dr. Eneas Carvalho Aguiar, 500 3° andar, 05403-000 São Paulo SP, Brazil. Phone and fax: 55-11-30829350. E-mail: luizagui{at}usp.br.

Infection and Immunity, September 2001, p. 5345-5351, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5345-5351.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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