Distinct CD4 - CD8 - (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease.
Autor: | Passos LSA; Departamento de Morfologia Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; Pós-graduação em Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Koh CC; Departamento de Morfologia Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Magalhães LMD; Departamento de Morfologia Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; Pós-graduação em Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Nunes MDCP; Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Gollob KJ; Hospital Israelita Albert Einstein, São Paulo, Brazil.; Instituto Nacional de Ciência e Tecnologia Doenças Tropicais-INCT-DT, Belo Horizonte, Brazil., Dutra WO; Departamento de Morfologia Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; Pós-graduação em Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; Instituto Nacional de Ciência e Tecnologia Doenças Tropicais-INCT-DT, Belo Horizonte, Brazil. |
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Jazyk: | angličtina |
Zdroj: | Frontiers in immunology [Front Immunol] 2021 Nov 11; Vol. 12, pp. 761795. Date of Electronic Publication: 2021 Nov 11 (Print Publication: 2021). |
DOI: | 10.3389/fimmu.2021.761795 |
Abstrakt: | CD4 - CD8 - (double-negative, DN) T cells are critical orchestrators of the cytokine network associated with the pathogenic inflammatory response in one of the deadliest cardiomyopathies known, Chagas heart disease, which is caused by Trypanosoma cruzi infection. Here, studying the distribution, activation status, and cytokine expression of memory DN T-cell subpopulations in Chagas disease patients without cardiac involvement (indeterminate form-IND) or with Chagas cardiomyopathy (CARD), we report that while IND patients displayed a higher frequency of central memory, CARD had a high frequency of effector memory DN T cells. In addition, central memory DN T cells from IND displayed a balanced cytokine profile, characterized by the concomitant expression of IFN-γ and IL-10, which was not observed in effector memory DN T cells from CARD. Supporting potential clinical relevance, we found that the frequency of central memory DN T cells was associated with indicators of better ventricular function, while the frequency of effector memory DN T cells was not. Importantly, decreasing CD1d-mediated activation of DN T cells led to an increase in IL-10 expression by effector memory DN T cells from CARD, restoring a balanced profile similar to that observed in the protective central memory DN T cells. Targeting the activation of effector memory DN T cells may emerge as a strategy to control inflammation in Chagas cardiomyopathy and potentially in other inflammatory diseases where these cells play a key role. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Passos, Koh, Magalhães, Nunes, Gollob and Dutra.) |
Databáze: | MEDLINE |
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