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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2014.tde-11072014-141421
Document
Author
Full name
Tiago Clemente Machado
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Rodrigues, Mauricio Martins (President)
Câmara, Niels Olsen Saraiva
Gil, Cristiane Damas
Mosig, Jose Maria Alvarez
Rosa, Daniela Santoro
Title in Portuguese
Novo papel da galectina-1 como molécula efetora de células citotóxicas.
Keywords in Portuguese
Célula NK
Células citotóxicas
Citotoxicidade celular
FAS-FASL
Galectina-1
Linfócito TCD8+
Lisossomos secretórios
Proliferação celular
Abstract in Portuguese
A exocitose de grânulos secretórios é o principal mecanismo efetor de células TCD8+. No entanto, pouco se sabe sobre a composição dos grânulos líticos dessas células. Resultados prévios do nosso grupo identificaram algumas dezenas de novas proteínas desses grânulos. Dentre elas foi identificada Gal-1. A literatura relata que Gal-1 age por via exógena através de sua secreção por via não convencional. Dados iniciais do nosso grupo apontam um novo cenário para esta proteína no qual ela está presente em grânulos citotóxicos. Através das técnicas de microscopia eletrônica e confocal e de ensaios de citotoxicidade, nossos resultados sugerem que Gal-1 participa do papel citotóxico das CTLs modulando a via dos receptores de morte FAS-FASL. Nós também mostramos que Gal-1 interfere com o tempo de contato entre APCs e linfócitos TCD8+, com a ativação dessas células e com o controle da proliferação dos linfócitos. Nossos resultados apontam um novo cenário para Gal-1, no qual ela está presente em grânulos líticos das CTLs e está relacionada a resposta efetora dessas células.
Title in English
New role for galectin-1 as effector molecule of cytotoxic cells.
Keywords in English
CD8+ T lymphocytes
Cell proliferation
Cellular cytotoxicity
Cytotoxic cells
FAS-FASL
Galectin-1
NK cell
Secretory lysosomes
Abstract in English
Exocytosis of secretory granules is the main effector mechanism of CD8+ T cells. In particular, little is known about CTLs lytic granules composition. Previous results from our group identified a few dozens of new proteins associated with these granules. Among them, we identified galectin-1. Literature reports the extracellular action of Gal-1. Initial data from our group suggested a new scenario for this protein, since Gal-1 was found inside cytotoxic granules. Here, we show by transmission electron and confocal laser scanning microscopy and cytotoxicity assays that Gal-1 has a role on CTL killing probably mediating the FAS-FASL pathway. We also show that Gal-1 is regulates the time of contact between APCs and TCD8+ lymphocytes, the activation of APCs and the proliferation of CD8 T cells. Taken together, our findings suggest a new scenario, in which Gal-1 is present in CTL granules and participates in cytotoxic effector response.
 
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Publishing Date
2014-07-11
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • CLEMENTE, T., et al. In vivo assessment of specific cytotoxic T lymphocyte killing [doi:10.1016/j.ymeth.2013.02.007]. Methods (San Diego, Calif., Print) [online], 2013, p. 105-109.
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