Gag-Specific CD4<sup>+</sup>T-Cell Frequency Is Inversely Correlated with Proviral Load and Directly Correlated with Immune Activation in Infection with Human Immunodeficiency Virus Type 2 (HIV-2) but Not HIV-1

Foxall, Russell B.; Cortesão, Catarina S.; Albuquerque, Adriana S.; Soares, Rui; Victorino, Rui M. M.; Sousa, Ana E.

doi:10.1128/jvi.01217-08

Cited by 18 publications

(11 citation statements)

References 31 publications

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“…This is consistent with other HIVspecific CD4 + T cell studies (26). For the Boolean gating analysis to detect multiple cytokine responses, values .0.01% and twice the background were considered as positive after background subtraction.…”

Section: Flow Cytometry Analysissupporting

confidence: 80%

A Steady State of CD4+ T Cell Memory Maturation and Activation Is Established during Primary Subtype C HIV-1 Infection

Maenetje¹,

Riou²,

Casazza

et al. 2010

The Journal of Immunology

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Section: Flow Cytometry Analysissupporting

confidence: 80%

A Steady State of CD4+ T Cell Memory Maturation and Activation Is Established during Primary Subtype C HIV-1 Infection

Maenetje¹,

Riou²,

Casazza

et al. 2010

The Journal of Immunology

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“…The relationship between HIV-induced immune responses and virological control remains contentious. Inverse correlations between HIV-specific T cell responses and concurrent plasma viral load have been demonstrated by some investigators [1], [2], [3], [4] but could not be confirmed by others [5], [6], [7], [8], [9]. Furthermore, some studies reported discordant correlations between T-cell responses and viral load and demonstrated these relationships to be determined by the infecting clade, targeting of sub-dominant epitopes [10], region of HIV targeted [4], [11], [12], and disease status [13].…”

Section: Introductionmentioning

confidence: 88%

Host HLA B*Allele-Associated Multi-Clade Gag T-Cell Recognition Correlates with Slow HIV-1 Disease Progression in Antiretroviral Therapy-Naïve Ugandans

et al. 2009

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BackgroundSome HIV infected individuals remain asymptomatic for protracted periods of time in the absence of antiretroviral therapy (ART). Virological control, CD4 T cell loss and HIV-specific responses are some of the key interrelated determinants of HIV-1 disease progression. In this study, possible interactions between viral load, CD4 T cell slopes, host genetics and HIV-specific IFN-γ responses were evaluated in chronically HIV-1-infected adults.Methodolology/Principal FindingsMultilevel regression modeling was used to stratify clade A or D HIV-infected individuals into disease progression groups based on CD4 T cell slopes. ELISpot assays were used to quantify the frequency and magnitude of HIV-induced IFN-γ responses in 7 defined rapid progressors (RPs) and 14 defined slow progressors (SPs) at a single time point. HLA typing was performed using reference strand conformational analysis (RSCA). Although neither the breadth nor the magnitude of the proteome-wide HIV-specific IFN-γ response correlated with viral load, slow disease progression was associated with over-representation of host immunogenetic protective HLA B* alleles (10 of 14 SPs compared to 0 of 7; p = 0.004, Fisher's Exact) especially B*57 and B*5801, multiclade Gag T-cell targeting (71%, 10 of 14 SPs compared to 14%, 1 of 7 RPs); p = 0.029, Fisher's Exact test and evident virological control (3.65 compared to 5.46 log10 copies/mL in SPs and RPs respectively); p<0.001, unpaired student's t-testConclusionsThese data are consistent with others that associated protection from HIV disease with inherent host HLA B allele-mediated ability to induce broader Gag T-cell targeting coupled with apparent virological control. These immunogenetic features of Gag-specific immune response which could influence disease progression may provide useful insight in future HIV vaccine design.

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“…However, progression to AIDS occurs in almost all untreated individuals, reflecting the inability of the immune system to mount effective, sustained responses. It has been clearly demonstrated that the overall magnitude of IFNγ-producing HIV-specific CD8+ T cells does not associate with viral control or the establishment of the viral set point (4–8). However, Betts and others have reported that long term non-progressors (LTNPs) were characterized by having higher frequencies of polyfunctional HIV-specific CD8+ T cells compared to non-controllers (9–12), introducing the concept that the quality, rather than the quantity, of antigen-specific T cell responses may dictate T-cell antiviral capacity and play a role in controlling viral replication.…”

Section: Introductionmentioning

confidence: 99%

Increased Memory Differentiation Is Associated with Decreased Polyfunctionality for HIV but Not for Cytomegalovirus-Specific CD8+ T Cells

Riou

Treurnicht

Abrahams

et al. 2012

The Journal of Immunology

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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 ART-naïve HIV-1 infected individuals at approximately 34 weeks post infection. These profiles were compared with CMV-specific CD8+ T cell responses in HIV-uninfected controls 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 mono-functional cells (p<0.001) compared to terminally-differentiated (CD45RO−CD27−) HIV-specific CD8+ T cells. The majority of terminally-differentiated HIV-specific CD8+ T cells were mono-functional (median 69% [IQR: 57–83]), producing predominantly CD107a or MIP1β. Moreover, proportions of HIV-specific mono-functional CD8+ T cells positively associated with proportions of terminally-differentiated 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.

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Gag-Specific CD4⁺T-Cell Frequency Is Inversely Correlated with Proviral Load and Directly Correlated with Immune Activation in Infection with Human Immunodeficiency Virus Type 2 (HIV-2) but Not HIV-1

Cited by 18 publications

References 31 publications

A Steady State of CD4+ T Cell Memory Maturation and Activation Is Established during Primary Subtype C HIV-1 Infection

A Steady State of CD4+ T Cell Memory Maturation and Activation Is Established during Primary Subtype C HIV-1 Infection

Host HLA B*Allele-Associated Multi-Clade Gag T-Cell Recognition Correlates with Slow HIV-1 Disease Progression in Antiretroviral Therapy-Naïve Ugandans

Increased Memory Differentiation Is Associated with Decreased Polyfunctionality for HIV but Not for Cytomegalovirus-Specific CD8+ T Cells

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Gag-Specific CD4+T-Cell Frequency Is Inversely Correlated with Proviral Load and Directly Correlated with Immune Activation in Infection with Human Immunodeficiency Virus Type 2 (HIV-2) but Not HIV-1

Cited by 18 publications

References 31 publications

A Steady State of CD4+ T Cell Memory Maturation and Activation Is Established during Primary Subtype C HIV-1 Infection

A Steady State of CD4+ T Cell Memory Maturation and Activation Is Established during Primary Subtype C HIV-1 Infection

Host HLA B*Allele-Associated Multi-Clade Gag T-Cell Recognition Correlates with Slow HIV-1 Disease Progression in Antiretroviral Therapy-Naïve Ugandans

Increased Memory Differentiation Is Associated with Decreased Polyfunctionality for HIV but Not for Cytomegalovirus-Specific CD8+ T Cells

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Gag-Specific CD4⁺T-Cell Frequency Is Inversely Correlated with Proviral Load and Directly Correlated with Immune Activation in Infection with Human Immunodeficiency Virus Type 2 (HIV-2) but Not HIV-1