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Doctoral Thesis
DOI
10.11606/T.42.2015.tde-06102015-135509
Document
Author
Full name
Jonatan Ersching
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Bortoluci, Karina Ramalho (President)
Bargieri, Bruna Cunha de Alencar
Kallas, Esper Georges
Lopes, Marcela de Freitas
Maugeri, Ieda Maria Longo
Title in Portuguese
Estudo das bases celulares e moleculares do controle da resposta imune mediada por linfócitos T CD8+ específicos durante a infecção experimental por Trypanosoma cruzi e vacinação com vetor adenoviral recombinante.
Keywords in Portuguese
Trypanosoma cruzi
Adenovírus
Foxp3
Imunoproteassomo
Linfócitos T CD8+
Vacina
Abstract in Portuguese
O controle da infecção por Trypanosoma cruzi dependente da resposta de linfócitos T CD8+. Porém, o parasito faz a indução subótima destes linfócitos, que pode ser corrigida pela vacinação genética. Não se sabe como T. cruzi induz uma resposta ruim dos linfócitos T CD8+, nem como a vacinação reverte esta resposta. Estas questões foram objeto de estudo da presente tese. O envolvimento do imunoproteassomo foi investigado na indução de imunidade in vivo em animais triplamente deficientes das subunidades 1i, 2i e 5i (TKO), indicando que o imunoproteassomo é essencial para o processamento dos epítopos de T. cruzi relacionados à imunidade protetora de linfócitos T CD8+ gerados durante a infecção e na vacinação. Também foi observado que T. cruzi, mas não adenovírus, é capaz de tornar uma resposta ótima de linfócitos transgênicos induzidos in vivo em subótima. A interferência do parasito envolveu a supressão ativa do priming dos linfócitos T CD8+ mediada por linfócitos T CD4+ CD25- Foxp3+ de modo independente de IL-10, mas parcialmente dependente de TGF- e CTLA-4.
Title in English
Study of the cellular and molecular basis of specific CD8+ T lymphocyte immune response control during experimental infection by Trypanosoma cruzi and vaccination with recombinant adenoviral vector.
Keywords in English
Trypanosoma cruzi
Adenovírus
CD8+ T lymphocytes
Foxp3
Immunoproteassome
Vaccine
Abstract in English
The control of infection by Trypanosoma cruzi relies on the response of CD8+ T cells. However, the parasite suboptimally induces these lymphocytes, which can be corrected by genetic vaccination. It is unknown how T. cruzi induces a poor response of CD8+ T cells and how vaccination reverts this. These questions were subject of study in this thesis. The involvement of the immunoproteasome was investigated in the in vivo induction of immunity in mice triply deficient of the subunits β1i, β2i e β5i (TKO), indicating that the immunoproteasome is essential for the processing of T. cruzi epitopes related to the protective immunity of CD8+ T cells generated upon infection and vaccination. Also, it was observed that T. cruzi, and not adenovirus, is capable of turning an optimal response of in vivo-induced transgenic CD8+ T cells into suboptimal. The parasite interference involved the active suppression of CD8+ T cell priming mediated by CD4+ CD25- Foxp3+ lymphocytes, in an IL-10-independent, but TGF-β and CTLA-4 partially dependent manner.
 
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Release Date
2017-10-05
Publishing Date
2015-10-16
 
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