Correlates of T-cell–mediated viral control and phenotype of CD8+ T cells in HIV-2, a naturally contained human retroviral infection

Silva, Thushan I. de; Peng, Yanchun; Leligdowicz, Aleksandra; Zaidi, Irfan; Li, L; Griffin, H. D.; M-E., Blais; Vincent, Tim; Saraiva, Margarida; Yindom, L M; Tienen, Carla van; Easterbrook, Philippa; Jaye, Assan; Whittle, Hilton; Dong, Tao; Rowland‐Jones, Sarah

doi:10.1182/blood-2012-12-472787

Cited by 49 publications

(45 citation statements)

References 47 publications

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“…However, no significant correlation was found in PD-1 high cells (r = 0.3308, p = 0.07, not shown). This indicates that PD-1 is preferentially up-regulated in HIV-specific cells as described elsewhere [33]–[35]. Also, regarding specific cells, no PD-1 expression difference was observed in cells with different specificities (i.e.…”

Section: Resultssupporting

confidence: 73%

Early Skewed Distribution of Total and HIV-Specific CD8+ T-Cell Memory Phenotypes during Primary HIV Infection Is Related to Reduced Antiviral Activity and Faster Disease Progression

et al. 2014

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The important role of the CD8+ T-cells on HIV control is well established. However, correlates of immune protection remain elusive. Although the importance of CD8+ T-cell specificity and functionality in virus control has been underscored, further unraveling the link between CD8+ T-cell differentiation and viral control is needed. Here, an immunophenotypic analysis (in terms of memory markers and Programmed cell death 1 (PD-1) expression) of the CD8+ T-cell subset found in primary HIV infection (PHI) was performed. The aim was to seek for associations with functional properties of the CD8+ T-cell subsets, viral control and subsequent disease progression. Also, results were compared with samples from Chronics and Elite Controllers. It was found that normal maturation of total and HIV-specific CD8+ T-cells into memory subsets is skewed in PHI, but not at the dramatic level observed in Chronics. Within the HIV-specific compartment, this alteration was evidenced by an accumulation of effector memory CD8+ T (TEM) cells over fully differentiated terminal effector CD8+ T (TTE) cells. Furthermore, higher proportions of total and HIV-specific CD8+ TEM cells and higher HIV-specific TEM/(TEM+TTE) ratio correlated with markers of faster progression. Analysis of PD-1 expression on total and HIV-specific CD8+ T-cells from PHI subjects revealed not only an association with disease progression but also with skewed memory CD8+ T-cell differentiation. Most notably, significant direct correlations were obtained between the functional capacity of CD8+ T-cells to inhibit viral replication in vitro with higher proportions of fully-differentiated HIV-specific CD8+ TTE cells, both at baseline and at 12 months post-infection. Thus, a relationship between preservation of CD8+ T-cell differentiation pathway and cell functionality was established. This report presents evidence concerning the link among CD8+ T-cell function, phenotype and virus control, hence supporting the instauration of early interventions to prevent irreversible immune damage.

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Section: Resultssupporting

confidence: 73%

Early Skewed Distribution of Total and HIV-Specific CD8+ T-Cell Memory Phenotypes during Primary HIV Infection Is Related to Reduced Antiviral Activity and Faster Disease Progression

et al. 2014

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“…In fact, measuring IFN-␥ only would have missed 60% of the responses to HIV (data not shown), with MIP-1␤ being the most abundant cytokine produced, in agreement with other studies (7). Our findings accord with recent data (17) showing that viral control of HIV-2 was significantly associated with a high-magnitude, polyfunctional Gag-specific CD8 ϩ T cell response. This further confirms the prevailing notion that immune responses to Gag possess enhanced antiviral potency compared to other specificities, likely as a result of its conservation and the higher rate of viral escape that exacts a fitness cost for HIV (18)(19)(20).…”

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confidence: 92%

Differential Impact of Magnitude, Polyfunctional Capacity, and Specificity of HIV-Specific CD8 ⁺ T Cell Responses on HIV Set Point

Riou

Burgers

Mlisana

et al. 2014

J Virol

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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.

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“…A polyfunctional T-cell response is associated with control of both HIV-1 and HIV-2, mycobacteria tuberculosis (latent disease), hepatitis C, as well as other infections (10,11,29). In addition, a polyfunctional cytokine response after vaccination is considered protective (30,31).…”

Section: Discussionmentioning

confidence: 99%

Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation

Snyder¹,

Chan²,

Kwon³

et al. 2016

Am J Respir Crit Care Med

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Rationale: Cytomegalovirus (CMV), which is one of the most common infections after lung transplantation, is associated with chronic lung allograft dysfunction and worse post-transplantation survival. Current approaches for at-risk patients include a fixed duration of antiviral prophylaxis despite the associated cost and side effects.Objectives: We sought to identify a specific immunologic signature that predicted protection from subsequent CMV.Methods: CMV-seropositive lung transplantation recipients were included in the discovery (n = 43) and validation (n = 28) cohorts. Polyfunctional CMV-specific immunity was assessed by stimulating peripheral blood mononuclear cells with CMV pp65 or IE-1 peptide pools and then by measuring T-cell expression of CD107a, IFN-g, tumor necrosis factor-a (TNF-a), and IL-2. Recipients were prospectively monitored for subsequent viremia. A Cox proportional hazards regression model that considered cytokine responses individually and in combination was used to create a predictive model for protection from CMV reactivation. This model was then applied to the validation cohort.Measurements and Main Results: Using the discovery cohort, we identified a specific combination of polyfunctional T-cell subsets to pp65 that predicted protection from subsequent CMV viremia (concordance index 0.88 [SE, 0.087]

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Correlates of T-cell–mediated viral control and phenotype of CD8+ T cells in HIV-2, a naturally contained human retroviral infection

Abstract: Key Points HIV-2 viral control is associated with a polyfunctional Gag-specific CD8+ T-cell response but not with perforin upregulation. Our findings provide insight into cellular immune responses associated with a naturally contained human retroviral infection.

Cited by 49 publications

References 47 publications

Early Skewed Distribution of Total and HIV-Specific CD8+ T-Cell Memory Phenotypes during Primary HIV Infection Is Related to Reduced Antiviral Activity and Faster Disease Progression

Early Skewed Distribution of Total and HIV-Specific CD8+ T-Cell Memory Phenotypes during Primary HIV Infection Is Related to Reduced Antiviral Activity and Faster Disease Progression

Differential Impact of Magnitude, Polyfunctional Capacity, and Specificity of HIV-Specific CD8 ⁺ T Cell Responses on HIV Set Point

Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation

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Correlates of T-cell–mediated viral control and phenotype of CD8+ T cells in HIV-2, a naturally contained human retroviral infection

Abstract: Key Points HIV-2 viral control is associated with a polyfunctional Gag-specific CD8+ T-cell response but not with perforin upregulation. Our findings provide insight into cellular immune responses associated with a naturally contained human retroviral infection.

Cited by 49 publications

References 47 publications

Early Skewed Distribution of Total and HIV-Specific CD8+ T-Cell Memory Phenotypes during Primary HIV Infection Is Related to Reduced Antiviral Activity and Faster Disease Progression

Early Skewed Distribution of Total and HIV-Specific CD8+ T-Cell Memory Phenotypes during Primary HIV Infection Is Related to Reduced Antiviral Activity and Faster Disease Progression

Differential Impact of Magnitude, Polyfunctional Capacity, and Specificity of HIV-Specific CD8 + T Cell Responses on HIV Set Point

Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation

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Differential Impact of Magnitude, Polyfunctional Capacity, and Specificity of HIV-Specific CD8 ⁺ T Cell Responses on HIV Set Point