Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/25801
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
Authors: 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
Affilliation: 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.
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.
Abstract: 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.
Keywords: Chagas Disease
Chagasic Thymic Atrophy
CD4+CD8+ T Cells
Severe Forms
Human disease
keywords: Doença de Chagas
Atrofia Tímica Chagásica
Células CD4 + CD8 + T
Humanos
Issue Date: 2011
Publisher: Public Library of Science
Citation: 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.
DOI: 10.1371/journal.pntd.0001268
ISSN: 1935-2727
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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