Browsing by Author "Riou, Catherine."

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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.
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.
Effect of antiretroviral therapy on the memory and activation profiles of B cells in HIV-infected African women.
(American Association of Immunologists., 2017) Tanko, Ramla F.; Soares, Andreia P.; Müller, Tracey L.; Garrett, Nigel Joel.; Samsunder, Natasha.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Riou, Catherine.; Burgers, Wendy A.
Abstract available in pdf.
Fluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression.
(American Society for Microbiology, 2010) Mlotshwa, Mandla.; Riou, Catherine.; Chopera, Denis Rutendo.; de Assis Rosa, Debra.; Ntale, Roman.; Treurnicht, Florette K.; Woodman, Zenda.; Werner, Lise.; van Loggerenberg, Francois.; Mlisana, Koleka Patience.; Williamson, Carolyn.; Gray, Clive M.; Abdool Karim, Salim Safurdeen.
Deciphering immune events during early stages of human immunodeficiency virus type 1 (HIV-1) infection is critical for understanding the course of disease. We characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-y) enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C infection in 53 individuals and associated temporal patterns of responses with disease progression in the first 12 months. There was a diverse pattern of T-cell recognition across the proteome, with the recognition of Nef being immunodominant as early as 3 weeks postinfection. Over the first 6 months, we found that there was a 23% chance of an increased response to Nef for every week postinfection (P = 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%). Responses to Env and regulatory proteins appeared to remain stable. Three temporal patterns of HIV-specific T-cell responses could be distinguished: persistent, lost, or new. The proportion of persistent T-cell responses was significantly lower (P = 0.0037) in individuals defined as rapid progressors than in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell responses were coincidental with autologous viral epitope escape. Regression analysis between the time to fixed viral escape and lost T-cell responses (r = 0.61; P = 0.019) showed a mean delay of 14 weeks after viral escape. Collectively, T-cell epitope recognition is not a static event, and temporal patterns of IFN-y-based responses exist. This is due partly to viral sequence variation but also to the recognition of invariant viral epitopes that leads to waves of persistent T-cell immunity, which appears to associate with slower disease progression in the first year of infection.
Human immunodeficiency virus-specific gamma interferon enzyme-linked immunospot assay responses targeting specific regions of the proteome during primary subtype C infection are poor predictors of the course of viremia and set point.
(American Society for Microbiology., 2008) Gray, Clive M.; Mlotshwa, Mandla.; Riou, Catherine.; Mathebula, Tiyani.; Mashishi, Tumelo.; Seoighe, Cathal.; Ngandu, Nobubelo K.; de Assis Rosa, Debra.; van Loggerenberg, Francois.; Morris, Lynn.; Mlisana, Koleka Patience.; Williamson, Carolyn.; Abdool Karim, Salim Safurdeen.
It is unknown whether patterns of human immunodeficiency virus (HIV)-specific T-cell responses during acute infection may influence the viral set point and the course of disease. We wished to establish whether the magnitude and breadth of HIV type 1 (HIV-1)-specific T-cell responses at 3 months postinfection were correlated with the viral-load set point at 12 months and hypothesized that the magnitude and breadth of HIV-specific T-cell responses during primary infection would predict the set point. Gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses across the complete proteome were measured in 47 subtype C HIV-1-infected participants at a median of 12 weeks postinfection. When corrected for amino acid length and individuals responding to each region, the order of recognition was as follows: Nef > Gag > Pol > Rev > Vpr > Env > Vpu > Vif > Tat. Nef responses were significantly (P < 0.05) dominant, targeted six epitopic regions, and were unrelated to the course of viremia. There was no significant difference in the magnitude and breadth of responses for each protein region with disease progression, although there was a trend of increased breadth (mean, four to seven pools) in rapid progressors. Correlation of the magnitude and breadth of IFN-γ responses with the viral set point at 12 months revealed almost zero association for each protein region. Taken together, these data demonstrate that the magnitude and breadth of IFN-γ ELISPOT assay responses at 3 months postinfection are unrelated to the course of disease in the first year of infection and are not associated with, and have low predictive power for, the viral set point at 12 months.
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.
Restoration of CD4+ responses to copathogens in HIV-infected individuals on antiretroviral therapy is dependent on T cell memory phenotype.
(American Association of Immunologists., 2015) Riou, Catherine.; Tanko, Ramla F.; Soares, Andreia P.; Masson, Lindi.; Werner, Lise.; Garrett, Nigel Joel.; Samsunder, Natasha.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Burgers, Wendy A.
Abstract available in pdf.
Vertical T cell immunodominance and epitope entropy determine HIV-1 escape.
(American Society for Clinical Investigation., 2012) Liu, Michael K. P.; Hawkins, Natalie.; Ritchie, Adam J.; Ganusov, Vitaly.; Whale, Victoria.; Brackenridge, Simon.; Li, Hui.; Pavlicek, Jeffrey W.; Cai, Fangping.; Abrahams, Melissa-Rose.; Treurnicht, Florette K.; Hraber, Peter.; Riou, Catherine.; Gray, Clive M.; Ferrari, Guido.; Tanner, Rachel.; Ping, Li-Hua.; Anderson, Jeffrey A.; Swanstrom, Ronald.; Cohen, Myron S.; Abdool Karim, Salim Safurdeen.; Haynes, Barton F.; Borrow, Persephone.; Perelson, Alan S.; Shaw, George M.; Hahn, Beatrice H.; Williamson, Carolyn.; Korber, Bette T. M.; Gao, Feng.; Self, Steven G.; McMichael, Andrew.; Goonetilleke, Nilu.
HIV-1 accumulates mutations in and around reactive epitopes to escape recognition and killing by CD8+ T cells. Measurements of HIV-1 time to escape should therefore provide information on which parameters are most important for T cell–mediated in vivo control of HIV-1. Primary HIV-1–specific T cell responses were fully mapped in 17 individuals, and the time to virus escape, which ranged from days to years, was measured for each epitope. While higher magnitude of an individual T cell response was associated with more rapid escape, the most significant T cell measure was its relative immunodominance measured in acute infection. This identified subject-level or “vertical” immunodominance as the primary determinant of in vivo CD8+ T cell pressure in HIV-1 infection. Conversely, escape was slowed significantly by lower population variability, or entropy, of the epitope targeted. Immunodominance and epitope entropy combined to explain half of all the variability in time to escape. These data explain how CD8+ T cells can exert significant and sustained HIV-1 pressure even when escape is very slow and that within an individual, the impacts of other T cell factors on HIV-1 escape should be considered in the context of immunodominance.