Functional state of CD4+ and CD8+ T lymphocytes and their role in the slow progression of HIV infection in pediatric patients

Miguel Antonio Alfonzo, Alexandra Diaz, Luigina Siciliano, Maria Graciela López, Alida Hung, Juan Felix Garcia
Jornal de Pediatria 2012, 88 (2): 161-8

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-alpha) and interferon gamma (IFN-gamma), besides measuring intracellular IFN-gamma 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-gamma producing CD4+ T lymphocytes (p < 0.05), and a smaller capacity of IL-10, TNF-alpha and IFN-gamma 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.

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