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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2016.tde-17112016-140922
Document
Author
Full name
Maria Alejandra Clavijo Salomon
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Barbuto, Jose Alexandre Marzagao (President)
Basso, Alexandre Salgado
Chammas, Roger
Lepique, Ana Paula
Sato, Maria Notomi
Title in Portuguese
Células Natural Killer na modulação da imunidade celular em humanos.
Keywords in Portuguese
Células dendríticas
Células Natural Killer
IFN-γ
Linfócitos T CD8
Monócitos
NKp30
Abstract in Portuguese
Células dendríticas (DCs) são componentes centrais da imunidade celular, responsáveis pelo priming de linfócitos T naïve. A polarização de linfócitos T é restrita aos sinais fornecidos durante a apresentação do antígeno. Além desses sinais, a origem e natureza de DCs que induzem diferentes perfis de linfócitos T não é totalmente compreendida. Foi investigada a capacidade de células Natural Killer (NK) de modular estágios iniciais da diferenciação de monócitos em DCs e de impactar na sua função de primar e polarizar linfócitos T naïve. DCs derivadas de monócitos pré-co-cultivados com células NK favorecem o priming de linfócitos T CD8 do tipo Tc1/Tc17, com potente capacidade de produção de IFN-γ. Este fenômeno foi dependente de interações longas via NKp30 e da maquinaria citotóxica de células NK desencadeada nas etapas inicias da sua interação com monócitos. Esta interação pode ter implicações na compreensão da imunidade mediada por linfócitos T CD8 e pode ser explorada para imunoterapia em que a produção de IFN-γ por células T CD8 é necessária ou exacerbada.
Title in English
Natural Killer cells in the modulation of cell-mediated immunity in humans.
Keywords in English
CD8 T cells
Dendritic cells
IFN-γ
Monocytes
Natural Killer cells
NKp30
Abstract in English
Dendritic cells (DCs) are central components of cellular immunity, responsible for the priming of naïve T cells. The polarization of T cells is restricted to signals provided during antigen presentation. Besides such signals, the origin and nature of DCs that induce different T cell profiles is not fully understood. The ability of natural killer cells (NK) to modulate early stages of monocytes differentiation into DCs and to impact on DCs function to prime and polarize naïve T cells was investigated. DCs derived from monocytes co-cultured with NK cells support the priming of type Tc1/Tc17 CD8 T cells with potent IFN-γ production capacity. NK cell-mediated cytotoxicity triggered at early stages of NKp30-dependent long-lasting monocytes-NK-cells interactions, mediated the mechanism by which this phenomenon occurred. This interaction may have implications in the understanding of CD8 T cell-mediated immunity and can be exploited for immunotherapy in which IFN-γ production by CD8 T cells is required or exacerbated.
 
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Publishing Date
2016-11-17
 
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