title: Association of HIV-specific and total CD8+ T memory phenotypes in subtype C HIV-1 infection with viral set point.
abstract: 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.
authors.affiliation: Division of Medical Virology, Faculty of Health Sciences, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Burgers
authors.forename: Catherine
authors.initials: C
authors.lastname: Riou
authors.forename: Mandla
authors.initials: M
authors.lastname: Mlotshwa
authors.forename: Pholo
authors.initials: P
authors.lastname: Maenetje
authors.forename: Debra
authors.initials: D
authors.lastname: de Assis Rosa
authors.forename: Jason
authors.initials: J
authors.lastname: Brenchley
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Richard
authors.initials: R
authors.lastname: Koup
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Guy
authors.initials: G
authors.lastname: de Bruyn
authors.forename: Salim Abdool
authors.initials: SA
authors.lastname: Karim
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: Clive M
authors.initials: CM
authors.lastname: Gray