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 < 0.01), a significantly reduced expression of CD127 (p < 0.01), and an augmented frequency of apoptosis (p < 0.01). Furthermore, T cells from these patients displayed a diminished capacity of mitogen proliferation (p < 0.05), a reduced percentage of IFN-γ producing CD4+ T lymphocytes (p < 0.05), and a smaller capacity of IL-10, TNF-α and IFN-γ production (p < 0.01) in comparison with SP and control patients. Conclusion:Our findings indicate that the decline of the normal T lymphocyte molecular and cellular responses is related to a rapid progression and a decreased resistance to HIV-1 infection in children. ResumoObjetivo: Avaliar o estado funcional dos linfócitos T CD4+ e CD8+ de pacientes pediátricos venezuelanos infectados pelo HIV-1. Métodos:As crianças foram agrupadas como progressoras rápidas (PRs) ou progressoras lentas (PLs), com base no quadro clínico. Para determinara funcionalidade dos linfócitos T CD4+ e CD8+, foram utilizadas técnicas de citometria de fluxo e caracterizados parâmetros de funcionalidade dessas células por meio de testes ex vivo como expressão de CD95/ Fas e de CD127 e frequência de apoptose. Além disso, determinamos, em células mononucleares de sangue periférico, a proliferação do HIV e a produção de interleucina-10 (IL-10), do fator de necrose tumoral alfa (TNF-α) e de interferon gama (IFN-γ), e também estimamos o IFN-γ intracelular em células T CD4+.Resultados: Nossos resultados indicam que vários mecanismos moleculares e celulares dos linfócitos T CD4+ e CD8+ tiveram piora nos PRs em comparação com PLs e controles. Ambos os tipos de linfócitos T dos PRs apresentaram aumento na expressão de CD95/Fas (p < 0,01), redução na expressão de CD127 (p < 0,01) e elevação na frequência de apoptose (p < 0,01). Além disso, as células T desses pacientes apresentaram diminuição na capacidade de proliferação mitogênica (p < 0,05), redução na porcentagem de linfócitos T CD4+ produtores de IFN-γ (p < 0,05) e menor capacidade de produção...
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