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Mémoire de Maîtrise
DOI
https://doi.org/10.11606/D.42.2015.tde-09122015-130521
Document
Auteur
Nom complet
Bruna Tereso Santillo
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2015
Directeur
Jury
Sumida, Telma Miyuki Oshiro (Président)
Bargieri, Bruna Cunha de Alencar
Salmazi, Karina Inácio Ladislau de Carvalho
Titre en portugais
Caracterização fenotípica e funcional de IFN-DCs derivadas de indivíduos infectados pelo HIV-1.
Mots-clés en portugais
Células dendríticas
HIV
Interferon tipo I
Vacina terapêutica
Resumé en portugais
A imunoterapia baseada em MoDC constitui uma estratégia para tratamento de indivíduos HIV+. Protocolos para obtenção de MoDC em geral utilizam IL-4 e GM-CSF (IL4-DC). Alguns estudos utilizam as IFN-DC (IFN-α + GM-CSF), que exibem um fenótipo combinado de DC mielóide, DC plasmocitóide (pDC) e célula NK. Esse perfil misto pode aperfeiçoar a imunoterapia para pacientes HIV+. Para tanto, monócitos de pacientes HIV+ foram cultivados com GM-CSF e IL-4 ou IFN-α por 5 dias e estimuladas por 48 horas com pulso de HIV inativado por AT-2 e/ou coquetel de citocinas pró-inflamatórias. Avaliamos a expressão de moléculas de superfície de IFN-DC e ativação de linfócitos T por citometria de fluxo; produção de citocinas IL-12 e IL-10 por ELISA. IFN-DC apresentaram morfologia e fenótipo basais ativados e características de pDC e célula NK, diferente das IL4-DC. As IFN-DC foram capazes de produzir IL-12, estimular a proliferação e produção de IFN-γ de linfócitos TCD4 e CD8, porém similares às IL4-DCs. IFN-DC são capazes de estimular resposta de linfócitos T tanto quanto IL4-DC.
Titre en anglais
Immunophenotypic and functional characterization of IFN-DC derived HIV-1 infected patients.
Mots-clés en anglais
Dendritic cells
HIV
Therapeutic vaccine
Type I Interferon
Resumé en anglais
Immunotherapy based on MDDCs is a strategy for treating HIV-infected patients. Alternatively to the conventional protocol for DC differentiation based on IL-4 and GM-CSF (IL4-DC) some studies suggest the use of IFN-DC (IFN-α + GM-CSF). These cells exhibit a combined phenotype of myeloid DC, plasmacytoid DC (pDC) and NK. Considering the mixed profile of IFN-DCs alternative protocols can bring novel elements for immunotherapy. Monocytes isolated from HIV-infected patients were cultured in the presence of GM-CSF and IL-4 or IFN-α. On day 5 DCs were pulsed with AT-2-inactivated HIV and stimulated for 48 hours with a cocktail of proinflammatory cytokines. We assessed IFN-DC surface markers expression and T cell activation by flow cytometry; IL-10 and IL-12 production by ELISA. IFN-DC showed activated morphological and phenotypic features during basal state of maturity and exhibited features of pDC and NK different from IL4-DC. The IFN-DC like IL4-DC were able to produce IL-12 and stimulated T cells. So, the IFN-DC were able to stimulate the T cells as well as IL4-DCs.
 
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Date de Publication
2015-12-09
 
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