Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease

Detalhes bibliográficos
Autor(a) principal: Morrot, Alexandre
Data de Publicação: 2011
Outros Autores: Granado, Eugênia Terra, Pérez, Ana Rosa, Barbosa, Suse Dayse Silva, Milićević, Novica M., Oliveira, Désio Aurélio Farias de, Berbert, Luiz Ricardo, Meis, Juliana de, Takiya, Christina Maeda, Beloscar, Juan, Wang, Xiaoping, Kont, Vivian, Peterson, Pärt, Bottasso, Oscar, Savino, Wilson
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/25801
Resumo: Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
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spelling Morrot, AlexandreGranado, Eugênia TerraPérez, Ana RosaBarbosa, Suse Dayse SilvaMilićević, Novica M.Oliveira, Désio Aurélio Farias deBerbert, Luiz RicardoMeis, Juliana deTakiya, Christina MaedaBeloscar, JuanWang, XiaopingKont, VivianPeterson, PärtBottasso, OscarSavino, Wilson2018-04-12T13:42:42Z2018-04-12T13:42:42Z2011MORROT, Alexandre; et al. Chagasic Thymic Atrophy Does Not Affect Negative Selection but Results in the Export of Activated CD4+CD8+ T Cells in Severe Forms of Human Disease. PLoS Negl Trop Dis., v.5, n.8, e1268, 13p, Aug. 2011.1935-2727https://www.arca.fiocruz.br/handle/icict/2580110.1371/journal.pntd.00012681935-2735engPublic Library of ScienceDoença de ChagasAtrofia Tímica ChagásicaCélulas CD4 + CD8 + THumanosChagas DiseaseChagasic Thymic AtrophyCD4+CD8+ T CellsSevere FormsHuman diseaseChagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human diseaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.National University of Rosario. School of Medical Sciences. Institute of Immunology. Rosario, Argentina.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Câncer. Departamento de Pesquisa Clínica. Rio de Janeiro, RJ, Brasil.University of Beograd. Faculty of Medicine. Institute of Histology and Embryology. Beograd, Servia.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Instituto Nacional de Ciência e Tecnologia de Fármacos e Medicamentos. Laboratório de Avaliação e Síntese de Substâncias Bioativas. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Patologia Celular. Rio de Janeiro, RJ, Brasil.National University of Rosario. School of Medical Sciences. Institute of Immunology. Rosario, Argentina.University of Tartu. Institute of General and Molecular Pathology. Molecular Pathology. Tartu, Estonia.University of Tartu. Institute of General and Molecular Pathology. Molecular Pathology. Tartu, Estonia.University of Tartu. Institute of General and Molecular Pathology. Molecular Pathology. Tartu, Estonia.National University of Rosario. School of Medical Sciences. Institute of Immunology. Rosario, Argentina.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Extrathymic CD4+CD8+ double-positive (DP) T cells are increased in some pathophysiological conditions, including infectious diseases. In the murine model of Chagas disease, it has been shown that the protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironment and the lymphoid compartment. In the acute phase, this results in a severe atrophy of the organ and early release of DP cells into the periphery. To date, the effect of the changes promoted by the parasite infection on thymic central tolerance has remained elusive. Herein we show that the intrathymic key elements that are necessary to promote the negative selection of thymocytes undergoing maturation during the thymopoiesis remains functional during the acute chagasic thymic atrophy. Intrathymic expression of the autoimmune regulator factor (Aire) and tissue-restricted antigen (TRA) genes is normal. In addition, the expression of the proapoptotic Bim protein in thymocytes was not changed, revealing that the parasite infection-induced thymus atrophy has no effect on these marker genes necessary to promote clonal deletion of T cells. In a chicken egg ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic system, the administration of OVA peptide into infected mice with thymic atrophy promoted OVA-specific thymocyte apoptosis, further indicating normal negative selection process during the infection. Yet, although the intrathymic checkpoints necessary for thymic negative selection are present in the acute phase of Chagas disease, we found that the DP cells released into the periphery acquire an activated phenotype similar to what is described for activated effector or memory single-positive T cells. Most interestingly, we also demonstrate that increased percentages of peripheral blood subset of DP cells exhibiting an activated HLA-DR+ phenotype are associated with severe cardiac forms of human chronic Chagas disease. These cells may contribute to the immunopathological events seen in the Chagas disease.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/25801/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALeugenia_granado_etal_IOC_2011.pdfeugenia_granado_etal_IOC_2011.pdfapplication/pdf5193562https://www.arca.fiocruz.br/bitstream/icict/25801/2/eugenia_granado_etal_IOC_2011.pdff4c9cfb7d394befeb3be742c57a40accMD52TEXTeugenia_granado_etal_IOC_2011.pdf.txteugenia_granado_etal_IOC_2011.pdf.txtExtracted texttext/plain66693https://www.arca.fiocruz.br/bitstream/icict/25801/3/eugenia_granado_etal_IOC_2011.pdf.txt2b3425fbb50e646acee280b76b0791abMD53icict/258012023-09-05 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dc.title.pt_BR.fl_str_mv Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease
title Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease
spellingShingle Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease
Morrot, Alexandre
Doença de Chagas
Atrofia Tímica Chagásica
Células CD4 + CD8 + T
Humanos
Chagas Disease
Chagasic Thymic Atrophy
CD4+CD8+ T Cells
Severe Forms
Human disease
title_short Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease
title_full Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease
title_fullStr Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease
title_full_unstemmed Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease
title_sort Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease
author Morrot, Alexandre
author_facet Morrot, Alexandre
Granado, Eugênia Terra
Pérez, Ana Rosa
Barbosa, Suse Dayse Silva
Milićević, Novica M.
Oliveira, Désio Aurélio Farias de
Berbert, Luiz Ricardo
Meis, Juliana de
Takiya, Christina Maeda
Beloscar, Juan
Wang, Xiaoping
Kont, Vivian
Peterson, Pärt
Bottasso, Oscar
Savino, Wilson
author_role author
author2 Granado, Eugênia Terra
Pérez, Ana Rosa
Barbosa, Suse Dayse Silva
Milićević, Novica M.
Oliveira, Désio Aurélio Farias de
Berbert, Luiz Ricardo
Meis, Juliana de
Takiya, Christina Maeda
Beloscar, Juan
Wang, Xiaoping
Kont, Vivian
Peterson, Pärt
Bottasso, Oscar
Savino, Wilson
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Morrot, Alexandre
Granado, Eugênia Terra
Pérez, Ana Rosa
Barbosa, Suse Dayse Silva
Milićević, Novica M.
Oliveira, Désio Aurélio Farias de
Berbert, Luiz Ricardo
Meis, Juliana de
Takiya, Christina Maeda
Beloscar, Juan
Wang, Xiaoping
Kont, Vivian
Peterson, Pärt
Bottasso, Oscar
Savino, Wilson
dc.subject.other.pt_BR.fl_str_mv Doença de Chagas
Atrofia Tímica Chagásica
Células CD4 + CD8 + T
Humanos
topic Doença de Chagas
Atrofia Tímica Chagásica
Células CD4 + CD8 + T
Humanos
Chagas Disease
Chagasic Thymic Atrophy
CD4+CD8+ T Cells
Severe Forms
Human disease
dc.subject.en.pt_BR.fl_str_mv Chagas Disease
Chagasic Thymic Atrophy
CD4+CD8+ T Cells
Severe Forms
Human disease
description Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
publishDate 2011
dc.date.issued.fl_str_mv 2011
dc.date.accessioned.fl_str_mv 2018-04-12T13:42:42Z
dc.date.available.fl_str_mv 2018-04-12T13:42:42Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv MORROT, Alexandre; et al. Chagasic Thymic Atrophy Does Not Affect Negative Selection but Results in the Export of Activated CD4+CD8+ T Cells in Severe Forms of Human Disease. PLoS Negl Trop Dis., v.5, n.8, e1268, 13p, Aug. 2011.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/25801
dc.identifier.issn.pt_BR.fl_str_mv 1935-2727
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pntd.0001268
dc.identifier.eissn.none.fl_str_mv 1935-2735
identifier_str_mv MORROT, Alexandre; et al. Chagasic Thymic Atrophy Does Not Affect Negative Selection but Results in the Export of Activated CD4+CD8+ T Cells in Severe Forms of Human Disease. PLoS Negl Trop Dis., v.5, n.8, e1268, 13p, Aug. 2011.
1935-2727
10.1371/journal.pntd.0001268
1935-2735
url https://www.arca.fiocruz.br/handle/icict/25801
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