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

dc.creatorMorrot, Alexandre
dc.creatorGranado, Eugênia Terra
dc.creatorPérez, Ana Rosa
dc.creatorBarbosa, Suse Dayse Silva
dc.creatorMilićević, Novica M.
dc.creatorOliveira, Désio Aurélio Farias de
dc.creatorBerbert, Luiz Ricardo
dc.creatorMeis, Juliana de
dc.creatorTakiya, Christina Maeda
dc.creatorBeloscar, Juan
dc.creatorWang, Xiaoping
dc.creatorKont, Vivian
dc.creatorPeterson, Pärt
dc.creatorBottasso, Oscar
dc.creatorSavino, Wilson
dc.date2018-04-12T13:42:42Z
dc.date2018-04-12T13:42:42Z
dc.date2011
dc.date.accessioned2023-09-26T20:26:10Z
dc.date.available2023-09-26T20:26:10Z
dc.identifierMORROT, 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.identifier1935-2727
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/25801
dc.identifier10.1371/journal.pntd.0001268
dc.identifier1935-2735
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8856853
dc.descriptionExtrathymic 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectDoença de Chagas
dc.subjectAtrofia Tímica Chagásica
dc.subjectCélulas CD4 + CD8 + T
dc.subjectHumanos
dc.subjectChagas Disease
dc.subjectChagasic Thymic Atrophy
dc.subjectCD4+CD8+ T Cells
dc.subjectSevere Forms
dc.subjectHuman disease
dc.titleChagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease
dc.typeArticle


Este ítem pertenece a la siguiente institución