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.
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 thym...
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ftdoajarticles:oai:doaj.org/article:2cb64136f2bd4361993f80d6f4d7d937 2023-05-15T15:16:13+02:00 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. Alexandre Morrot Eugênia Terra-Granado Ana Rosa Pérez Suse Dayse Silva-Barbosa Novica M Milićević Désio Aurélio Farias-de-Oliveira Luiz Ricardo Berbert Juliana De Meis Christina Maeda Takiya Juan Beloscar Xiaoping Wang Vivian Kont Pärt Peterson Oscar Bottasso Wilson Savino 2011-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001268 https://doaj.org/article/2cb64136f2bd4361993f80d6f4d7d937 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3156684?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 doi:10.1371/journal.pntd.0001268 1935-2727 1935-2735 https://doaj.org/article/2cb64136f2bd4361993f80d6f4d7d937 PLoS Neglected Tropical Diseases, Vol 5, Iss 8, p e1268 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001268 2022-12-31T13:53:28Z 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 ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 8 e1268 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Alexandre Morrot Eugênia Terra-Granado Ana Rosa Pérez Suse Dayse Silva-Barbosa Novica M Milićević Désio Aurélio Farias-de-Oliveira Luiz Ricardo Berbert Juliana De Meis Christina Maeda Takiya Juan Beloscar Xiaoping Wang Vivian Kont Pärt Peterson Oscar Bottasso Wilson Savino 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. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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 ... |
format |
Article in Journal/Newspaper |
author |
Alexandre Morrot Eugênia Terra-Granado Ana Rosa Pérez Suse Dayse Silva-Barbosa Novica M Milićević Désio Aurélio Farias-de-Oliveira Luiz Ricardo Berbert Juliana De Meis Christina Maeda Takiya Juan Beloscar Xiaoping Wang Vivian Kont Pärt Peterson Oscar Bottasso Wilson Savino |
author_facet |
Alexandre Morrot Eugênia Terra-Granado Ana Rosa Pérez Suse Dayse Silva-Barbosa Novica M Milićević Désio Aurélio Farias-de-Oliveira Luiz Ricardo Berbert Juliana De Meis Christina Maeda Takiya Juan Beloscar Xiaoping Wang Vivian Kont Pärt Peterson Oscar Bottasso Wilson Savino |
author_sort |
Alexandre Morrot |
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. |
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. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001268 https://doaj.org/article/2cb64136f2bd4361993f80d6f4d7d937 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 8, p e1268 (2011) |
op_relation |
http://europepmc.org/articles/PMC3156684?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 doi:10.1371/journal.pntd.0001268 1935-2727 1935-2735 https://doaj.org/article/2cb64136f2bd4361993f80d6f4d7d937 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001268 |
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PLoS Neglected Tropical Diseases |
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5 |
container_issue |
8 |
container_start_page |
e1268 |
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1766346510583201792 |