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J Immunol. 2009 Apr 15;182(8):4751-61. doi: 10.4049/jimmunol.0803801.

Association of HIV-specific and total CD8+ T memory phenotypes in subtype C HIV-1 infection with viral set point.

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Division of Medical Virology, Faculty of Health Sciences, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.


Understanding early immunological events during HIV-1 infection that may set the course of disease progression is important for identifying correlates of viral control. This study explores the association of differentiation profiles of HIV-specific and total memory CD8(+) T cells with viral set point. A cohort of 47 HIV-1-infected individuals, with differing viral set points at 12 mo, were recruited during acute infection. We identified that the magnitude of IFN-gamma(+) T cell responses at 6 mo postinfection did not associate with viral set point at 12 mo. A subset of 16 individuals was further studied to characterize CD8(+) T cells for expression patterns of markers for memory differentiation, survival (CD127), senescence (CD57), and negative regulation (programmed death-1). We show that viral control and the predicted tempo of HIV disease progression in the first year of infection was associated with a synchronous differentiation of HIV-specific and total CD8(+) memory subpopulations. At 6-9 mo postinfection, those with low viral set points had a significantly higher proportion of early differentiated HIV-specific and total memory CD8(+) cells of a central memory (CD45RO(+)CD27(+)CCR7(+)) and intermediate memory (CD45RO(-)CD27(+)CCR7(-)) phenotype. Those with high viral set points possessed significantly larger frequencies of effector memory (CD45RO(+)CD27(-)CCR7(-)) cells. The proportions of memory subsets significantly correlated with CD38(+)CD8(+) T cells. Thus, it is likely that a high Ag burden resulting in generalized immune activation may drive differentiation of HIV-specific and total memory CD8(+) T cells.

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