Abstract
AbstractChagas disease is a neglected tropical disease in Latin America and an imported emerging disease worldwide. Chronic Chagas disease cardiomyopathy (CCC) is the most prominent clinical form and can lead to heart failure, thromboembolism, and sudden death. While previous reports have supported a role for CD4+ T lymphocytes in the pathogenesis of CCC a comprehensive analysis of these cells during different clinical forms is lacking. Here, we used high-dimensional flow cytometry to assess the diversity of circulating CD4+ T cells in patients with distinct clinical forms. We found increased frequencies of CD4+CD69+ T cells in patients compared to controls. CD39+ regulatory T cells, represented by mesocluster 6 were reduced in mild CCC patients compared to controls. Cytotoxic CD4+ T cells co-expressing granzyme B and perforin were expanded in patients with Chagas disease and were higher in patients with mild CCC compared to controls. Furthermore, patients with mild CCC displayed higher frequencies of multifunctional effector memory CD4+ T cells. Our results demonstrate an expansion in activated CD4+ T cells and a decrease in a functional subset of regulatory T cells associated with the onset of Chagas cardiomyopathy, suggesting their role in the establishment of cardiac lesions and as potential biomarkers for disease aggravation.
Funder
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Fundação de Amparo à Pesquisa do Estado de Minas Gerais
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference54 articles.
1. Dias JCP, Ramos AN, Gontijo ED, Luquetti A, Shikanai-Yasuda MA, Coura JR, et al. 2nd Brazilian Consensus on Chagas disease, 2015. Rev Soc Bras Med Trop. 2016;49:3–60.
2. Shikanai-Yasuda MA, Carvalho NB. Oral transmission of chagas disease. Clin Infect Dis. 2012;54:845–52.
3. Angheben A, Boix L, Buonfrate D, Gobbi F, Bisoffi Z, Pupella S, et al. Chagas disease and transfusion medicine: a perspective from non-endemic countries. Blood Transfus. 2015;13:540–50.
4. Martins-Melo FR, Ramos Junior AN, Alencar CH, Heukelbach J. Multiple causes of death related to Chagas’ disease in Brazil, 1999 to 2007. Rev Soc Bras Med Trop. 2012;45:591–6.
5. Higuchi MD. Endomyocardial biopsy in Chagas’ heart disease: pathogenetic contributions. Sao Paulo Med J. 1995;113:821–5.
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