Caracterización de la funcionalidad y el fenotipo de linfocitos T CD8+ en individuos HIV-1 positivos bajo tratamiento antirretroviral combinado

Several strategies have been proposed in the quest for an HIV cure, many rely on CD8+ T cells (CD8TC) antiviral activity. In this thesis, the functionality and phenotype of in vitro expanded HIV-specific CD8TC, obtained from HIV+ subjects on combined antiretroviral treatment (cART), was investigated...

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Detalles Bibliográficos
Autor principal: Salido, Jimena Patricia
Otros Autores: Malchiodi, Emilio
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2019
Materias:
HIV
Remisión virológica
LTCD8+
Expandidos
Polifuncionalidad y fenotipo
Actividad antiviral
Tiempo de inicio del cART
Inmunología
Viral remission
Expanded
CD8+ T-cell response
Polyfunctionality and phenotype
Antiviral activity
Time of cART initiation
Ciencias de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2824
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2824.dir/2824.PDF
Aporte de:
Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Several strategies have been proposed in the quest for an HIV cure, many rely on CD8+ T cells (CD8TC) antiviral activity. In this thesis, the functionality and phenotype of in vitro expanded HIV-specific CD8TC, obtained from HIV+ subjects on combined antiretroviral treatment (cART), was investigated. According to the momento of cART initiation, two groups were recruited: early treatment (TTe) or delayed treatment (TTa) groups. Peripheral blood mononuclear cells were obtained and expanded using Nef and Gag peptide pools. Post-expansion, CD8TC specificity, functionality, memory phenotype differentiation, PD-1 expression, as well as antiviral activity were assessed. Even though, post-cART HIV specific immune response results deeply diminished, it could be selectively expanded, demonstrating a polifunctional and effector memory/effector profiles, as well as strong antiviral activity. Differences in cART initiation timing affected mainly memory phenotype differentiation, possibly reflecting the impact of antigenic stimulation on the immune system. In both groups, characteristics of the immune response observed before cART could be proposed as biomarkers of the functionality of CD8TC that persist post-cART. In sum, these results have important implications in the design of strategies aimed at boosting CD8TC beneficial responses.

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