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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2014.tde-15122014-162230
Document
Author
Full name
Raquel Müller Gonçalves Lopes
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Ferreira, Marcelo Urbano (President)
Antonelli, Lis Ribeiro do Valle
Bortoluci, Karina Ramalho
Marinho, Claudio Romero Farias
Soares, Irene da Silva
Title in Portuguese
Caracterização de linfócitos T CD4+ que expressam moléculas reguladoras e fontes celulares de interleucina 10 na malária humana.
Keywords in Portuguese
Citocinas
Fontes celulares de IL-10
Linfócitos T CD4+ reguladores
Málaria humana
Abstract in Portuguese
Além das células T reguladoras clássicas (Treg), fenotipicamente definidas como CD4+CD25highCD127-FOXP3+, outros subtipos celulares que expressam moléculas reguladoras e produzem IL-10 podem desempenhar papel imunomodulador na malária humana. Caracterizamos subpopulações celulares que expressam marcadores de ativação celular e de atividade reguladora em indivíduos infectados por P. falciparum, P. vivax ou co-infectados com ambas as espécies, bem como em controles saudáveis de uma área endêmica de malária na Amazônia Brasileira. Mostramos que a malária induz duas subpopulações principais de células T reguladoras, uma expressando CTLA-4 (uma molécula de superfície que inibe a ativação de células T) e outra expressando OX40, uma molécula co-estimulatória que pode suprimir a atividade supressora da Treg. Mostramos que diferentes populações de PBMCs, provenientes de pacientes com malária e controles saudáveis, produzem IL-10 após a estimulação ex vivo com phorbol-12-myristate-13-acetate (PMA) e ionomicina em comparação com o estímulo com lipopolissacarídeo (LPS).
Title in English
Characterization of T CD4+ lymphocytes expressing regulatory molecules and cellular sources of interleukin 10 in human malaria.
Keywords in English
Cellular sources of IL-10
Cytokines
Human malária
Regulatory CD4+ T cell
Abstract in English
Besides classical regulatory T cells (Treg), which are phenotypically defined as CD4+CD25highCD127-FOXP3+, other cell subtypes expressing regulatory molecules and producing IL-10 may play an immunomodulatory role in human malaria. We characterized cell subpopulations that express markers of cell activation and regulatory activity in individuals infected with P. falciparum, P. vivax, or co-infected with both species, as well as in healthy controls from a malária-endemic area in the Brazilian Amazon. We show that malaria induces two major subpopulations of regulatory T cells, expressing CTLA-4 (a surface molecule that inhibits the activation of T cells) and another expressing OX40 (a co-stimulatory molecule that can suppress the suppressive activity of Treg). We showed that different populations of PBMCs from malaria patients and healthy controls, produce IL-10 after ex-vivo stimulation with phorbol-12-myristate-13-acetate (PMA) and ionomycin, compared to stimulation with lipopolysaccharide (LPS).
 
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Publishing Date
2014-12-16
 
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