Estado funcional dos linfócitos T CD4+ e CD8+ e seu papel na progressão lenta da infecção por HIV em pacientes pediátricos

OBJETIVO: Avaliar o estado funcional dos linfocitos T CD4+ e CD8+ de pacientes pediatricos venezuelanos infectados pelo HIV-1. METODOS: As criancas foram agrupadas como progressoras rapidas (PRs) ou progressoras lentas (PLs), com base no quadro clinico. Para determinar a funcionalidade dos linfocitos T CD4+ e CD8+, foram utilizadas tecnicas de citometria de fluxo e caracterizados parâmetros de funcionalidade dessas celulas por meio de testes ex vivo como expressao de CD95/Fas e de CD127 e frequencia de apoptose. Alem disso, determinamos, em celulas mononucleares de sangue periferico, a proliferacao do HIV e a producao de interleucina-10 (IL-10), do fator de necrose tumoral alfa (TNF-α) e de interferon gama (IFN-γ), e tambem estimamos o IFN-γ intracelular em celulas T CD4+. RESULTADOS: Nossos resultados indicam que varios mecanismos moleculares e celulares dos linfocitos T CD4+ e CD8+ tiveram piora nos PRs em comparacao com PLs e controles. Ambos os tipos de linfocitos T dos PRs apresentaram aumento na expressao de CD95/Fas (p OBJECTIVE: To evaluate simultaneously the functional state of CD4+ and CD8+ T lymphocytes from Venezuelan HIV-1-infected pediatric patients. METHODS: Children were assigned to subgroups of rapid progressors (RPs) and slow progressors (SPs), based on clinical features. To determine the degree of CD4+ and CD8+ T-lymphocyte functionality, flow cytometry techniques were used, and diverse parameters of the functionality of these cells were characterized by ex vivo tests, such as expression of CD95/Fas and CD127, and frequency of apoptosis. In addition, we determined, in cultured peripheral blood mononuclear cells, HIV-specific proliferation and the production of interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), besides measuring intracellular IFN-γ in CD4+ T cells. RESULTS: Our results indicate that several molecular and cellular mechanisms of CD4+ and CD8+ T lymphocytes are deteriorated in RPs in comparison with SPs and controls. Indeed, both types of T lymphocytes from RPs exhibited an increased expression of CD95/Fas (p