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Master's Dissertation
DOI
Document
Author
Full name
Maryanne Melanie Gonzales Carazas
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Mendes, Joao Gustavo Pessini Amarante (President)
Rodrigues, Elaine Guadelupe
Rosa, Daniela Santoro
Strauss, Bryan Eric
Title in Portuguese
Papel de BIM na geração de linfócitos T CD8+ antígeno-específicos, em resposta à vacinação com adenovírus recombinante.
Keywords in Portuguese
Adenovírus
Apoptose
BIM
Linfócitos T CD8+
Vacinação
Abstract in Portuguese
BIM é uma proteína pro-apoptótica membro da família Bcl-2. No sistema imunológico, BIM foi descrita como reguladora da homeostase de linfócitos. Porém, ainda não foi estudado o papel do BIM no estabelecimento da resposta imune de linfócitos T CD8+. Sendo que os vetores adenovirais fortes ativadores da resposta, neste trabalho investigamos o papel de BIM na qualidade e frequência de linfócitos T CD8+ estimulados com Ad.cOVA. Camundongos C57Bl/6 selvagens, bim+/- e bim-/- foram imunizados com 2x106 PFU/100μl. Assim, observou-se uma redução da lise especifica e menor freqüência de linfócitos CD8+ produtores de IFNγ em camundongos bim-/-. Em paralelo, foi avaliada a resposta imune anti-tumoral destes camundongos sem encontrar diferencias significativas. A cinética da resposta efetora de linfócitos T CD8+ de camundongos bim-/- mostrou escassa perda das capacidades efetoras destes linfócitos, sendo o possível mecanismo para controlar a progressão tumoral. Em conclusão camundongos bim-/- apresentam uma menor freqüência de células efetoras, sugerindo um importante papel de BIM na produção de linfócitos T CD8+ antígeno-específicos trás a vacinação com Ad.cOVA.
Title in English
Role of BIM in the generation of antigen-specific CD8+ T lymphocytes in response to vaccination with recombinant adenovirus.
Keywords in English
Adenovirus
Apoptosis
BIM
CD8+ T lymphocytes
Vaccination
Abstract in English
BIM is a pro-apoptotic member of the Bcl-2 protein family. In the immune system, BIM has been described as lymphocyte homeostasis regulator. However, the role of BIM in the establishment of the immune response of CD8+ T lymphocytes has not yet been studied. As the strong adenoviral vectors activating the response, we investigated the role of BIM in the quality and frequency of Ad.cOVA-stimulated CD8+ T lymphocytes. Wild C57Bl/6 mice, bim+/- and bim-/- were immunized with 2x106 PFU/100μl. Thus, a reduction of the specific lysis and decreased frequency of IFNγ producing CD8+ lymphocytes in bim-/- mice was observed. In parallel, the anti-tumor immune response of these mice was evaluated without finding significant differences. The kinetics of the effector response of CD8+ T lymphocytes from bim-/- mice showed little loss of the effector capacities of these lymphocytes, being the possible mechanism to control tumor progression. In conclusion, bim-/- mice show a lower frequency of effector cells, suggesting an important role of BIM in the production of antigen-specific CD8+ T lymphocytes after vaccination with Ad.cOVA.
 
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Release Date
2019-07-12
Publishing Date
2017-07-12
 
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