Browsing by Author "Koup, Richard A."

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Association of HIV-Specific and Total CD8+ T Memory Phenotypes in Subtype C HIV-1 Infection with Viral Set Point.
(The American Association of Immunologists, Inc., 2009) Burgers, Wendy A.; Riou, Catherine.; Mlotshwa, Mandla.; Maenetje, Pholo.; de Assis Rosa, Debra.; Brenchley, Jason.; Mlisana, Koleka Patience.; Douek, Daniel C.; Koup, Richard A.; Roederer, Mario.; De Bruyn, Guy.; Abdool Karim, Salim Safurdeen.; Williamson, Carolyn.; Gray, Clive M.
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-γ+ 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.
Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge.
(American Association for the Advancement of Science., 2017) Julg, Boris.; Tartaglia, Lawrence J.; Keele, Brandon F.; Wagh, Kshitij.; Pegu, Amarendra.; Sok, Devin.; Abbink, Peter.; Schmidt, Stephen D.; Wang, Keyun.; Chen, Xuejun.; Joyce, M. Gordon.; Georgiev, Ivelin S.; Choe, Misook.; Kwong, Peter D.; Doria-Rose, Nicole A.; Le, Khoa.; Louder, Mark K.; Bailer, Robert T.; Moore, Penelope L.; Korber, Bette T. M.; Seaman, Michael S.; Abdool Karim, Salim Safurdeen.; Morris, Lynn.; Koup, Richard A.; Mascola, John R.; Burton, Dennis R.; Barouch, Dan H.
Abstract available in pdf.
Differential impact of magnitude, polyfunctional capacity, and specificity of HIV-specific CD8+ T cell responses on HIV set point.
(American Society for Microbiology., 2014) Riou, Catherine.; Burgers, Wendy A.; Mlisana, Koleka Patience.; Roederer, Mario.; Abdool Karim, Salim Safurdeen.; Williamson, Carolyn.; Gray, Clive M.; Koup, Richard A.
Defining the characteristics of HIV-specific CD8(+) T cell responses that lead to viral control is crucial for vaccine development. We evaluated the differential impact of magnitude, polyfunctional capacity, and specificity of the CD8(+) response at approximately 6 months postinfection on the viral set point at 12 months in a cohort of HIV-infected individuals. High frequencies of Gag and Nef responses endowed with four functions were the best predictors of a low viral set point.
Increased memory differentiation is associated with decreased polyfunctionality for HIV but not for CMV-specific CD8+ T cells.
(American Association of Immunologists., 2012) Riou, Catherine.; Treurnicht, Florette K.; Abrahams, Melissa-Rose.; Mlisana, Koleka Patience.; Liu, Michael K. P.; Goonetilleke, Nilu.; Koup, Richard A.; Roederer, Mario.; Abdool Karim, Salim Safurdeen.; De Bruyn, Guy.; Williamson, Carolyn.; Gray, Clive M.; Burgers, Wendy A.
The generation of polyfunctional CD8+ T cells, in response to vaccination or natural infection, has been associated with improved protective immunity. However, it is unclear whether the maintenance of polyfunctionality is related to particular cellular phenotypic characteristics. To determine whether the cytokine expression profile is linked to the memory differentiation stage, we analyzed the degree of polyfunctionality of HIV-specific CD8+ T cells within different memory subpopulations in 20 antiretroviral therapy-naive HIV-1–infected individuals at ∼34 wk postinfection. These profiles were compared with CMV-specific CD8+ T cell responses in HIV-uninfected control subjects and in individuals chronically infected with HIV. Our results showed that the polyfunctional abilities of HIV-specific CD8+ T cells differed according to their memory phenotype. Early-differentiated cells (CD45RO+CD27+) exhibited a higher proportion of cells positive for three or four functions (p < 0.001), and a lower proportion of monofunctional cells (p < 0.001) compared with terminally differentiated (TD; CD45RO-CD27-) HIV-specific CD8+ T cells. The majority of TD HIV-specific CD8+ T cells were monofunctional (median 69% [interquartile range: 57–83]), producing predominantly CD107a or MIP1b. Moreover, proportions of HIV-specific monofunctional CD8+ T cells positively associated with proportions of TD HIV-specific CD8+ T cells (p = 0.019, r = 0.54). In contrast, CMV-specific CD8+ T cell polyfunctional capacities were similar across all memory subpopulations, with terminally and early-differentiated cells endowed with comparable polyfunctionality. Overall, these data show that the polyfunctional abilities of HIV-specific CD8+ T cells are influenced by the stage of memory differentiation, which is not the case for CMV-specific responses.