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From Innate to Acquired Immune Response
a Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil b Institute for Immunology Investigation, Millennium Institute, São Paulo, Brazil c Clinical Immunology and Allergy, Department of Clinical Medicine, University of São Paulo, School of Medicine, São Paulo, Brazil
Key Words: autoimmune disease • rheumatic fever • molecular mimicry • T lymphocytes • genetic polymorphism • cytokines
Address for correspondence: Luiza Guilherme, Laboratório de Imunologia, Instituto do Coração (HC-FMUSP), Av. Dr. Eneas de Carvalho Aguiar, 44-9 andar, 05403-000 São Paulo, São Paulo, Brazil. Voice: +55-11-3069-5901; fax: +55-11-3069-5953. luizagui{at}usp.br
Rheumatic fever (RF) is triggered by S. pyogenes and affects 3–4% of untreated susceptible children. The immune response against streptococcal antigens can lead cross-recognition of heart tissue proteins resulting in rheumatic heart disease (RHD). HLA class II alleles have been associated with the development of RF/RHD. Tumor necrosis factor (TNF)-
 is also located in the same chromosomal region of HLA genes and has been investigated in RHD patients from Mexico, Turkey, and Brazil. Associations with the TNFA-308 allele were found and probably are related to the development of valvular lesions. A deficient mannose-binding lectin (MBL) allele was found in Brazilian patients. MBL is a protein important for the first line of host defense against the bacteria. The association with diverse genes probably indicates a role of certain molecules in both the innate and adaptive immune response. Antigen-presenting cells bearing the HLA-DR7 molecule from RHD patients preferentially recognized a heart-tissue protein cross-reactive M5 (81–96) peptide. The same peptide was also recognized by heart tissue T cell clones. Cardiac myosin peptides were recognized by high numbers of intralesional T cell clones. The cytokine pattern of infiltrating mononuclear cells in both myocardium and valvular tissue showed a predominance of proinflammatory cytokines (TNF- and IFN- ) and scarce production of regulatory cytokines, such as IL-4, in the valve tissue. IL-10, a predominant regulatory cytokine, was also secreted by large numbers of cells in both valve and myocardium tissue. Data here indicate the complexity of immune reactions leading to autoimmune lesions in RF/RHD.
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