T cell mimicry in inflammatory heart disease.

Abstract

Inflammatory heart diseases such as myocarditis and rheumatic heart disease result from the infiltration of the myocardium or valve with T cells and macrophages that result in scarring of the myocardium or valve and alteration in cardiac function. Our studies of T cells from these diseases have identified cardiac myosin in both rheumatic carditis and myocarditis as an important autoantigen. In rheumatic heart disease, streptococcal M protein specific T cells migrate to valves. By investigating streptococcal M protein and cardiac myosin in the Lewis rat model of myocarditis and valvulitis, T cell mimicry is supported as a potential mechanism in disease. Structural and immunological mimicry between the streptococcal M protein and cardiac myosin is shown directly in the Lewis rat model. Rat T cell lines demonstrate mimicry between cardiac myosin and M protein, and T cells isolated directly from inflammatory lesions in myocarditis respond to streptococcal M protein peptides. Studies in BALB/c mice also support the immunological crossreactivity of T cells primed against cardiac myosin with streptococcal M protein peptides containing cardiac myosin homologies. T cell lines produced from the Lewis rat specific to the cardiac myosin like sequences of streptococcal M protein migrated to the valves after passive transfer of the M protein specific T cell lines. In coxsackieviral myocarditis in the MRL mouse strain, cardiac myosin mimicking M protein peptide NT4 was found to induce tolerance and prevent coxsackieviral induced myocarditis, suggesting T cell mimicry between coxsackievirus and streptococcal M protein, both of which are associated with inflammatory heart disease. T cell mimicry between cardiac myosin and microbial antigens such as the streptococcal M protein may prime the immune system for inflammatory heart disease.

• Authors: Madeleine W Cunningham
• Journal: Molecular immunology (Mol Immunol) Vol. 40 Issue 14-15 Pg. 1121-7 (Feb 2004) ISSN: 0161-5890 [Print] England
• PMID: 15036918 (Publication Type: Journal Article, Review)

Chemical References

• Antigens, Bacterial
• Bacterial Outer Membrane Proteins
• Carrier Proteins
• streptococcal M protein
• Cardiac Myosins

Topics

• Animals
• Antigens, Bacterial
• Autoimmunity (immunology)
• Bacterial Outer Membrane Proteins (immunology)
• Cardiac Myosins (immunology)
• Carrier Proteins (immunology)
• Enterovirus (immunology)
• Humans
• Mice
• Molecular Mimicry (immunology)
• Myocarditis (immunology)
• Rats
• T-Lymphocytes (immunology)