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   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  
   
نویسنده morrot a. ,terra-granado e. ,pérez a.r. ,silva-barbosa s.d. ,milićević n.m. ,farias-de-oliveira d.a. ,berbert l.r. ,de meis j. ,takiya c.m. ,beloscar j. ,wang x. ,kont v. ,peterson p. ,bottasso o. ,savino w.
منبع plos neglected tropical diseases - 2011 - دوره : 5 - شماره : 8
چکیده    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. © 2011 morrot et al.
آدرس department of immunology,microbiology institute,federal university of rio de janeiro,rio de janeiro,brazil,laboratory on thymus research,oswaldo cruz institute,oswaldo cruz foundation,rio de janeiro, Brazil, laboratory on thymus research,oswaldo cruz institute,oswaldo cruz foundation,rio de janeiro, Brazil, institute of immunology,school of medical sciences,national university of rosario,rosario, Argentina, laboratory on thymus research,oswaldo cruz institute,oswaldo cruz foundation,rio de janeiro,brazil,department of clinical research,national cancer institute,rio de janeiro, Brazil, institute of histology and embryology,faculty of medicine,university of beograd,beograd, Serbia, laboratory on thymus research,oswaldo cruz institute,oswaldo cruz foundation,rio de janeiro, Brazil, laboratory on thymus research,oswaldo cruz institute,oswaldo cruz foundation,rio de janeiro, Brazil, laboratory on thymus research,oswaldo cruz institute,oswaldo cruz foundation,rio de janeiro, Brazil, biomedical science institute,cell pathology laboratory,federal university of rio de janeiro,rio de janeiro, Brazil, institute of immunology,school of medical sciences,national university of rosario,rosario, Argentina, molecular pathology,institute of general and molecular pathology,university of tartu,tartu, Estonia, molecular pathology,institute of general and molecular pathology,university of tartu,tartu, Estonia, molecular pathology,institute of general and molecular pathology,university of tartu,tartu, Estonia, institute of immunology,school of medical sciences,national university of rosario,rosario, Argentina, laboratory on thymus research,oswaldo cruz institute,oswaldo cruz foundation,rio de janeiro, Brazil
 
     
   
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