(Circulation. 1995;92:415-420.)
© 1995 American Heart Association, Inc.
Articles |
Human Heart–Infiltrating T-Cell Clones From Rheumatic Heart Disease Patients Recognize Both Streptococcal and Cardiac Proteins
From the Instituto do Coração do Hospital das Clinicas, Faculdade de Medicina da Universidade de São Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.).
Correspondence to Jorge Kalil, MD, PhD, Laboratório de Imunologia de Transplantes, Instituto do Coração, Faculdade de Medicina USP, Av Dr Eneas de Carvalho Aguiar, 500-3° Andar, 05403-000 São Paulo, Brazil.
Background ß-Hemolytic streptococcal infection in developing countries still causes thousands of cases of rheumatic heart disease, demanding surgical valve correction. Antigenic mimicry between self and streptococcal components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility. Although heart streptococcal–M protein cross-reactive antibodies have been demonstrated, heart tissue damage seems to be T lymphocyte–dependent. We studied the infiltrating T lymphocytes in rheumatic heart lesions with the aim of understanding the role of cellular immune response at the site of the lesions.
Methods and Results We obtained 107 T-cell clones from surgical fragments of cardiac tissue from four rheumatic heart disease patients. We tested their capacity to recognize streptococcal M protein–derived synthetic peptides and heart proteins. We found eight infiltrating T-cell clones from all four patients that simultaneously recognize streptococcal M and heart proteins. Among the M-protein sequences tested, only synthetic peptides corresponding to regions 1 through 25, 81 through 103, and 163 through 177 were simultaneously recognized with heart protein fractions. Interestingly, regions 81 through 103 and 163 through 177 have been known to bear heart cross-reactive epitopes at the antibody level. Five of these clones are CD4+, and one is CD8+.
Conclusions The presence of heart–M protein cross-reactive T-cell clones in rheumatic heart lesions suggests their direct involvement in the pathogenesis of this disease. The dissection of protective and pathogenic epitopes of streptococcal M protein is an important step in allowing the development of a safe anti-streptococcal synthetic vaccine.
Key Words: autoimmunity • rheumatic heart disease • T cell clones • molecular mimicry • group A ß-hemolytic streptococci
This article has been cited by other articles:
 |
|
 |
|
  D. Gorton, B. Govan, C. Olive, and N. Ketheesan B- and T-Cell Responses in Group A Streptococcus M-Protein- or Peptide-Induced Experimental Carditis Infect. Immun., May 1, 2009; 77(5): 2177 - 2183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ramasawmy, G. S. Spina, K. C. Fae, A. C. Pereira, R. Nisihara, I. J. Messias Reason, M. Grinberg, F. Tarasoutchi, J. Kalil, and L. Guilherme Association of Mannose-Binding Lectin Gene Polymorphism but Not of Mannose-Binding Serine Protease 2 with Chronic Severe Aortic Regurgitation of Rheumatic Etiology Clin. Vaccine Immunol., June 1, 2008; 15(6): 932 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Blank, I. Krause, L. Magrini, G. Spina, J. Kalil, S. Jacobsen, H. J. Thiesen, M. W. Cunningham, L. Guilherme, and Y. Shoenfeld Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome Rheumatology, July 1, 2006; 45(7): 833 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Fae, D. D. da Silva, S. E. Oshiro, A. C. Tanaka, P. M. A. Pomerantzeff, C. Douay, D. Charron, A. Toubert, M. W. Cunningham, J. Kalil, et al. Mimicry in Recognition of Cardiac Myosin Peptides by Heart-Intralesional T Cell Clones from Rheumatic Heart Disease J. Immunol., May 1, 2006; 176(9): 5662 - 5670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. J. Ellis, Y. Li, W. Hildebrand, V. A. Fischetti, and M. W. Cunningham T Cell Mimicry and Epitope Specificity of Cross-Reactive T Cell Clones from Rheumatic Heart Disease J. Immunol., October 15, 2005; 175(8): 5448 - 5456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Blank, A Aron-Maor, and Y Shoenfeld From rheumatic fever to Libman-Sacks endocarditis: is there any possible pathogenetic link? Lupus, September 1, 2005; 14(9): 697 - 701. [Abstract] [PDF]
|
|
|
|
 |
|
 C. A.C. Abreu Filho, L. A.F. Lisboa, L. A.O. Dallan, G. S. Spina, M. Grinberg, M. Scanavacca, E. A. Sosa, J. A. F. Ramires, and S. A. Oliveira Effectiveness of the Maze Procedure Using Cooled-Tip Radiofrequency Ablation in Patients With Permanent Atrial Fibrillation and Rheumatic Mitral Valve Disease Circulation, August 30, 2005; 112(9_suppl): I-20 - I-25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Guilherme, P. Cury, L. M.F. Demarchi, V. Coelho, L. Abel, A. P. Lopez, S. E. Oshiro, S. Aliotti, E. Cunha-Neto, P. M.A. Pomerantzeff, et al. Rheumatic Heart Disease: Proinflammatory Cytokines Play a Role in the Progression and Maintenance of Valvular Lesions Am. J. Pathol., November 1, 2004; 165(5): 1583 - 1591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Galvin, M. E. Hemric, S. D. Kosanke, S. M. Factor, A. Quinn, and M. W. Cunningham Induction of Myocarditis and Valvulitis in Lewis Rats by Different Epitopes of Cardiac Myosin and Its Implications in Rheumatic Carditis Am. J. Pathol., January 1, 2002; 160(1): 297 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Brandt, P. J. Yarwood, D. J. McMillan, H. Vohra, B. Currie, L. Mammo, S. Pruksakorn, J. Saour, and M. F. Good Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations Int. Immunol., October 1, 2001; 13(10): 1335 - 1343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Guilherme, S. E. Oshiro, K. C. Fae, E. Cunha-Neto, G. Renesto, A. C. Goldberg, A. C. Tanaka, P. M. A Pomerantzeff, M. H. Kiss, C. Silva, et al. T-Cell Reactivity against Streptococcal Antigens in the Periphery Mirrors Reactivity of Heart-Infiltrating T Lymphocytes in Rheumatic Heart Disease Patients Infect. Immun., September 1, 2001; 69(9): 5345 - 5351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Davidson and B. Diamond Autoimmune Diseases N. Engl. J. Med., August 2, 2001; 345(5): 340 - 350. [Full Text] [PDF]
|
|
|
|
|
|
M. W. Cunningham Cardiac Myosin and the TH1/TH2 Paradigm in Autoimmune Myocarditis Am. J. Pathol., July 1, 2001; 159(1): 5 - 12. [Full Text] [PDF]
|
|
|
|
|
|
A. Quinn, S. Kosanke, V. A. Fischetti, S. M. Factor, and M. W. Cunningham Induction of Autoimmune Valvular Heart Disease by Recombinant Streptococcal M Protein Infect. Immun., June 1, 2001; 69(6): 4072 - 4078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Portugal, I. Dozmorov, I. Sidorov, I. Marrero, J. A. Fonseca, M. Spadafora-Ferreira, J. Kalil, and V. Coelho Renal transplant patients show variations in their self-reactive repertoires: a serial study Int. Immunol., June 1, 2001; 13(6): 747 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Brandt, T. Teh, W. A. Relf, R. I. Hobb, and M. F. Good Protective and Nonprotective Epitopes from Amino Termini of M Proteins from Australian Aboriginal Isolates and Reference Strains of Group A Streptococci Infect. Immun., December 1, 2000; 68(12): 6587 - 6594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. F. Jones, S. S. Whitehead, M. W. Cunningham, and V. A. Fischetti Reactivity of Rheumatic Fever and Scarlet Fever Patients' Sera with Group A Streptococcal M Protein, Cardiac Myosin, and Cardiac Tropomyosin: a Retrospective Study Infect. Immun., December 1, 2000; 68(12): 7132 - 7136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Cunningham Pathogenesis of Group A Streptococcal Infections Clin. Microbiol. Rev., July 1, 2000; 13(3): 470 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Guilherme, N. Dulphy, C. Douay, V. Coelho, E. Cunha-Neto, S. E. Oshiro, R. V Assis, A. C. Tanaka, P. M. Alberto Pomerantzeff, D. Charron, et al. Molecular evidence for antigen-driven immune responses in cardiac lesions of rheumatic heart disease patients Int. Immunol., July 1, 2000; 12(7): 1063 - 1074. [Abstract] [Full Text] [PDF]
|
|