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Doctoral Thesis
DOI
10.11606/T.42.2010.tde-11012011-150838
Document
Author
Full name
Lucas da Silva Faustino
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Russo, Momtchilo (President)
Câmara, Niels Olsen Saraiva
Faria, Ana Maria Caetano de
Keller, Alexandre de Castro
Silva, João Santana da
Title in Portuguese
Células T reguladoras na asma experimental.
Keywords in Portuguese
Asma
Células sanguíneas
Doenças imunológicas
Experimentos
Imunologia
Imunoparasitologia
Imunopatologia
Abstract in Portuguese
Células T reguladoras (Treg) são cruciais na tolerância periférica e no controle da inflamação. Nós usamos dois modelos bem estabelecidos de tolerância de mucosas para a asma alérgica e a tolerância inalatória local induzida pela exposição crônica a OVA para estudar o aparecimento e função das Treg. Nós mostramos que a tolerância nasal distinguiu da tolerância oral pela produção sistêmica de IgG1 e desenvolvimento da inflamação alérgica na cavidade peritoneal ou pela indução da inflamação das vias aéreas de camundongos RAG-/- reconstituídos com células T CD4+ após desafios com OVA. Observamos também que Treg Foxp3+ migraram para o pulmão alérgico e expressaram fenótipo de ativação e memória que distinguiu essas células das Treg presentes nos linfonodos drenantes. Células T CD4+CD25+ do pulmão dos animais alérgicos suprimiram a proliferação das células T CD4+CD25-, mas não a produção de citocinas Th2. Finalmente, a exposição crônica a OVA levou ao aumento da apoptose de eosinófilos que infiltraram o pulmão resultando na resolução da inflamação alérgica pulmonar.
Title in English
Regulatory T cells in the experimental asthma.
Keywords in English
Asthma
Blood cells
Experiments
Immune disorders
Immunology
Immunoparasitology
Immunopathology
Abstract in English
Regulatory T cells (Treg) are critical for peripheral tolerance and control of inflammation. We used two well established models of mucosal tolerance to allergic airway disease and the local inhalational tolerance induced by chronic OVA exposure to study the appearance and function of Treg cells. We found that nasal tolerance distinguished from oral tolerance by systemic IgG1 antibody production and development of allergic inflammation in the peritoneal cavity or by induction of airway inflammation in RAG-/- mice reconstituted with CD4+ T cells after OVA challenge. We also found that Foxp3+ T cells migrated to allergic lung and expressed an effector/memory phenotype that distinguished them from Treg cells present in lung draining lymph nodes. Lung infiltrating CD4+CD25+ T cells from allergic mice suppressed CD4+CD25- T cell proliferation but not Th2 cytokines production by these cells. Finally, chronic OVA exposure leaded to increased apoptosis of infiltrating lung eosinophils resulting in the resolution of allergic lung inflammation.
 
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Publishing Date
2011-05-16
 
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