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Distinct CD4(−)CD8(−) (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease

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, ac...

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Autores principales: Passos, Livia Silva Araújo, Koh, Carolina Cattoni, Magalhães, Luísa Mourão Dias, Nunes, Maria do Carmo Pereira, Gollob, Kenneth John, Dutra, Walderez Ornelas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632628/
https://www.ncbi.nlm.nih.gov/pubmed/34868005
http://dx.doi.org/10.3389/fimmu.2021.761795
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author Passos, Livia Silva Araújo
Koh, Carolina Cattoni
Magalhães, Luísa Mourão Dias
Nunes, Maria do Carmo Pereira
Gollob, Kenneth John
Dutra, Walderez Ornelas
author_facet Passos, Livia Silva Araújo
Koh, Carolina Cattoni
Magalhães, Luísa Mourão Dias
Nunes, Maria do Carmo Pereira
Gollob, Kenneth John
Dutra, Walderez Ornelas
author_sort Passos, Livia Silva Araújo
collection PubMed
description 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.
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spelling pubmed-86326282021-12-02 Distinct CD4(−)CD8(−) (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease Passos, Livia Silva Araújo Koh, Carolina Cattoni Magalhães, Luísa Mourão Dias Nunes, Maria do Carmo Pereira Gollob, Kenneth John Dutra, Walderez Ornelas Front Immunol Immunology 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. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8632628/ /pubmed/34868005 http://dx.doi.org/10.3389/fimmu.2021.761795 Text en Copyright © 2021 Passos, Koh, Magalhães, Nunes, Gollob and Dutra https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Passos, Livia Silva Araújo
Koh, Carolina Cattoni
Magalhães, Luísa Mourão Dias
Nunes, Maria do Carmo Pereira
Gollob, Kenneth John
Dutra, Walderez Ornelas
Distinct CD4(−)CD8(−) (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title Distinct CD4(−)CD8(−) (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title_full Distinct CD4(−)CD8(−) (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title_fullStr Distinct CD4(−)CD8(−) (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title_full_unstemmed Distinct CD4(−)CD8(−) (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title_short Distinct CD4(−)CD8(−) (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title_sort distinct cd4(−)cd8(−) (double-negative) memory t-cell subpopulations are associated with indeterminate and cardiac clinical forms of chagas disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632628/
https://www.ncbi.nlm.nih.gov/pubmed/34868005
http://dx.doi.org/10.3389/fimmu.2021.761795
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