Integrative Analysis of Immunological Data to Explore Chronic Immune T-Cell Activation in Successfully Treated HIV Patients

Picat, Marie-Quitterie; Pellegrin, Isabelle; Bitard, Juliette; Wittkop, Linda; Proust‐Lima, Cécile; Liquet, Benoit; Moreau, Jean-François; Bonnet, Fabrice; Blanco, Patrick; Thiébaut, Rodolphe

doi:10.1371/journal.pone.0169164

Cited by 5 publications

(5 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous studies, increased CMV-specific CD8+ T-cell responses has been associated with higher proportions of activated CD8+ T-cells (HLA-DR+/CD38+/CD8+) in PLWHIV on cART 15 , 22 . In addition, a high CMV IgG response has been associated with monocyte activation (sCD14) 20 , 41 .…”

Section: Discussionmentioning

confidence: 82%

See 1 more Smart Citation

Cytomegalovirus-specific T-cells are associated with immune senescence, but not with systemic inflammation, in people living with HIV

Ballegaard

Braendstrup

Pedersen

et al. 2018

Sci Rep

View full text Add to dashboard Cite

In people living with HIV (PLWHIV), coinfection with cytomegalovirus (CMV) has been associated with inflammation, immunological ageing, and increased risk of severe non-AIDS related comorbidity. The effect of CMV-specific immune responses on systemic inflammation, immune activation and T-cell senescence was evaluated in 53 PLWHIV treated with combination antiretroviral therapy (cART). Activated-, terminally differentiated-, naïve-, and senescent T-cells were assessed by flow cytometry, and plasma levels of CMV IgG, interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein and soluble-CD14 were measured. In PLWHIV, expression of interleukin-2, tumor necrosis factor-α and interferon-γ was measured by intracellular-cytokine-staining after stimulation of T-cells with CMV-pp65, CMV-IE1, and CMV-gB. Increased CMV-specific T-cell responses were associated with a higher ratio of terminally differentiated/naïve CD8+ T-cells and with increased proportions of senescent CD8+ T-cells, but not with systemic inflammation or sCD14. Increased CMV-specific CD4+ T-cell responses were associated with increased proportions of activated CD8+ T-cells. In PLWHIV with expansion of CMV-specific T-cells or increased T-cell senescence, CMV-specific polyfunctionality was maintained. That the magnitude of the CMV-specific T-cell response was associated with a senescent immune phenotype, suggests that a dysregulated immune response against CMV may contribute to the immunological ageing often described in PLWHIV despite stable cART.

show abstract

Section: Discussionmentioning

confidence: 82%

“…However, we found an association between increased CMV-specific CD4+ T-cell responses and higher proportions of activated CD8+ T-cells. Notably, previous studies did not investigate CMV-specific CD4+ T-cell responses 15 , 22 .…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus-specific T-cells are associated with immune senescence, but not with systemic inflammation, in people living with HIV

Ballegaard

Braendstrup

Pedersen

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…While this limits the scope of the current study, it nevertheless provides sufficient data for proof of concept that bacterial genera, species and strain discrimination using the host immune response is possible; (ii) the choice of bacterial collection within a species could be better defined and include E. coli strains from bacteraemia patients; (iii) the relatively small number of blood donors (n = 5) is sufficient for proof of concept but does not describe the variation in host response in a healthy population [1]. Finally, it is clear that more advanced multivariate analysis and modelling approaches used to determine cytokine interdependencies and networks may also provide a rational next step for biomarker discovery [103][104][105][106].…”

Section: Discussionmentioning

confidence: 99%

Using the Traditional Ex Vivo Whole Blood Model to Discriminate Bacteria by Their Inducible Host Responses

Chick,

Rees,

Lewis

et al. 2024

Biomedicines

View full text Add to dashboard Cite

Whole blood models are rapid and versatile for determining immune responses to inflammatory and infectious stimuli, but they have not been used for bacterial discrimination. Staphylococcus aureus, S. epidermidis and Escherichia coli are the most common causes of invasive disease, and rapid testing strategies utilising host responses remain elusive. Currently, immune responses can only discriminate between bacterial ‘domains’ (fungi, bacteria and viruses), and very few studies can use immune responses to discriminate bacteria at the species and strain level. Here, whole blood was used to investigate the relationship between host responses and bacterial strains. Results confirmed unique temporal profiles for the 10 parameters studied: IL-6, MIP-1α, MIP-3α, IL-10, resistin, phagocytosis, S100A8, S100A8/A9, C5a and TF3. Pairwise analysis confirmed that IL-6, resistin, phagocytosis, C5a and S100A8/A9 could be used in a discrimination scheme to identify to the strain level. Linear discriminant analysis (LDA) confirmed that (i) IL-6, MIP-3α and TF3 could predict genera with 95% accuracy; (ii) IL-6, phagocytosis, resistin and TF3 could predict species at 90% accuracy and (iii) phagocytosis, S100A8 and IL-10 predicted strain at 40% accuracy. These data are important because they confirm the proof of concept that host biomarker panels could be used to identify bacterial pathogens.

show abstract

“…Picat et al. ( 9 ) used ODEs to study the effects of IL-7 injections on T-cell dynamics in HIV-infected patients. Picat et al.…”

Section: Introductionmentioning

confidence: 99%

“…Picat et al. ( 9 ) used machine learning to study chronic immune T-cell activation in successfully treated HIV patients. Both studies used mathematical modeling and data analysis techniques to investigate immune responses in humans and have potential implications for the treatment of HIV infection and other immune-related conditions.…”

Section: Introductionmentioning

confidence: 99%

Modeling antibody dynamics following herpes zoster indicates that higher varicella-zoster virus viremia generates more VZV-specific antibodies

et al. 2023

View full text Add to dashboard Cite

IntroductionStudying antibody dynamics following re-exposure to infection and/or vaccination is crucial for a better understanding of fundamental immunological processes, vaccine development, and health policy research.MethodsWe adopted a nonlinear mixed modeling approach based on ordinary differential equations (ODE) to characterize varicella-zoster virus specific antibody dynamics during and after clinical herpes zoster. Our ODEs models convert underlying immunological processes into mathematical formulations, allowing for testable data analysis. In order to cope with inter- and intra-individual variability, mixed models include population-averaged parameters (fixed effects) and individual-specific parameters (random effects). We explored the use of various ODE-based nonlinear mixed models to describe longitudinally collected markers of immunological response in 61 herpes zoster patients.ResultsStarting from a general formulation of such models, we study different plausible processes underlying observed antibody titer concentrations over time, including various individual-specific parameters. Among the converged models, the best fitting and most parsimonious model implies that once Varicella-zoster virus (VZV) reactivation is clinically apparent (i.e., Herpes-zoster (HZ) can be diagnosed), short-living and long-living antibody secreting cells (SASC and LASC, respectively) will not expand anymore. Additionally, we investigated the relationship between age and viral load on SASC using a covariate model to gain a deeper understanding of the population’s characteristics.ConclusionThe results of this study provide crucial and unique insights that can aid in improving our understanding of VZV antibody dynamics and in making more accurate projections regarding the potential impact of vaccines.

show abstract

Integrative Analysis of Immunological Data to Explore Chronic Immune T-Cell Activation in Successfully Treated HIV Patients

Cited by 5 publications

References 68 publications

Cytomegalovirus-specific T-cells are associated with immune senescence, but not with systemic inflammation, in people living with HIV

Cytomegalovirus-specific T-cells are associated with immune senescence, but not with systemic inflammation, in people living with HIV

Using the Traditional Ex Vivo Whole Blood Model to Discriminate Bacteria by Their Inducible Host Responses

Modeling antibody dynamics following herpes zoster indicates that higher varicella-zoster virus viremia generates more VZV-specific antibodies

Contact Info

Product

Resources

About