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Doctoral Thesis
DOI
10.11606/T.42.2013.tde-07062014-103754
Document
Author
Full name
Mariana Ribeiro Dominguez
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Rodrigues, Mauricio Martins (President)
Bellio, Maria
Mosig, Jose Maria Alvarez
Rigato, Paula Ordonhez
Romero, Oscar Bruna
Title in Portuguese
Importância da resposta aos epítopos subdominantes, da proliferação e da recirculação de linfócitos T CD8+ durante a vacinação experimental contra a infecção pelo Trypanosoma cruzi.
Keywords in Portuguese
Adenovirus
Citocinas
Linfócitos B
Linfócitos T
Proliferação celular
Vacinação
Abstract in Portuguese
Neste trabalho nós estudamos qual seria o impacto da indução de resposta imune a epítopos CD8 subdominantes na imunidade gerada pela vacinação genética. Durante a infecção experimental apenas um epítopo imunodominante presente no antígeno ASP-2 é reconhecido. Já os linfócitos T CD8+ induzidos nos animais vacinados com o gene da ASP-2 são capazes de reconhecer além deste mais dois outros epítopos (subdominantes). A identificação desses epítopos permitiu que estudássemos o papel da resposta imune a epítopos subdominantes na imunidade protetora. Após imunização genética com o gene da ASP-2 mutado, sem resposta para o epítopo dominante, confirmamos que a resposta imune aos epítopos subdomiantes pode contribuir na proteção contra a infecção experimental. Apesar do papel critico dos linfócitos T CD8+ na resposta imune protetora induzida pela vacinação genética do tipo imunização e reforço heterólogo, não se sabe ao certo se após o desafio experimental estes linfócitos T CD8+ necessitam proliferar ou recircular para mediar a imunidade protetora. Nossos resultados desafiam o paradigma de ação das vacinas tradicionais de que a imunidade é dependente da proliferação e não da recircular dos linfócitos T de memória e para mediar a imunidade protetora.
Title in English
Importance of the response to subdominant epitope, proliferation and recirculation of CD8+ T lymphocytes during experimental vaccination against Trypanosoma cruzi infection.
Keywords in English
Adenovirus
B lymphocytes
Cell proliferation
Cytokines
T lymphocytes
Vaccination
Abstract in English
In the present study, we evaluated the impact of the immune response to sub-dominant CD8 epitopes on immunity generated by genetic vaccination. During experimental infection only a single dominant epitope is recognized on the antigen ASP-2. In contrast, the CD8+ T lymphocytes induced in animals genetically vaccinated with ASP-2 recognized, in addition to the dominant epitope, two other epitopes (sub-dominants). The identification of these epitopes allowed us to test the role of immune response to sub-dominant epitopes in protective immunity. After genetic vaccination with ASP-2 mutated gene, without the response to dominant epitope, we concluded that the immune response to the sub-dominant epitopes can be important to protective immunity. In spite of the critical role of CD8+ T lymphocytes in protective immune response induced by genetic vaccination using the heterologous prime-boost regimen, it is unclear whether after the experimental challenge these CD8+ T lymphocytes need to proliferate or recirculate to mediate protective immunity. Our results challenge the paradigm of action of traditional vaccines that immunity is dependent on the proliferation of memory T lymphocytes and that these cells do not need to recirculate.
 
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Publishing Date
2014-06-11
 
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