CD4+CD25+CD127− assessment as a surrogate phenotype for FOXP3+ regulatory T cells in HIV‐1 infected viremic and aviremic subjects

Saison, Julien; Demaret, Julie; Venet, Fabienne; Chidiac, Christian; Malcus, Christophe; Poitevin-Later, Françoise; Tardy, J.; Ferry, Tristan; Monneret, Guillaume

doi:10.1002/cyto.b.21047

Cited by 27 publications

(21 citation statements)

References 22 publications

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“…There is still controversy about CD4 + CD25 + CD127 low/– and CD4 + CD25 + FoxP3 + identifying the same subset of Treg cells; however, a recent study published in Cytometry has confirmed that both subsets can be used to identify Tregs. 32 Our results show that HIV-infected patients had a significantly higher percentage of Tregs than the controls. This is consistent with previous studies that have shown an increase of Treg cells in HIV-infected patients.…”

Section: Discussionmentioning

confidence: 50%

HIV and Tuberculosis co-infection impacts T-cell activation markers but not the numbers subset of regulatory T-cells in HIV-1 infected patients

et al. 2013

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BackgroundTuberculosis (TB) has been shown to accelerate the clinical course of HIV infection, but the mechanisms by which this occurs are not well understood. Regulatory T-cells (Tregs) are known to dampen hyperactivation of the immune cells, but it remains unclear whether hyperactivation of T-cells in HIV infection is associated with a decrease of Tregs and what the effect Mycobacterium tuberculosis (MTB) co-infection has on T-cell activation and Tregs.ObjectivesIn this study, we aim to evaluate whether active TB is associated with the increased expression of T-cell activation markers and reduced number of Treg cells in HIV-1-infected patients.MethodsThis study was conducted on 69 subjects consisting of 20 HIV-infected patients, 20 HIV and MTB co-infected patients, 19 MTB-infected patients and 10 uninfected control subjects negative for both MTB and HIV. The frequencies of T-cell activation markers (CD38 and HLA-DR) and Treg cells (CD4+CD25+CD127-) were measured by flow cytometry.ResultsSignificantly higher expression of CD38 and HLA-DR on CD4+ and CD8+ T-cells was found in MTB and HIV co-infected patients compared with HIV-infected patients. However, no significant difference in the percentage of Treg cells was reported between HIV patients with TB and those without. The study also showed a negative correlation between regulatory T-cells frequency and CD4+ T-cell counts.ConclusionThese results suggest that TB enhances the expression of peripheral T-cell activation markers during HIV infection, whilst having no impact on the percentages of Treg cells.

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Section: Discussionmentioning

confidence: 50%

HIV and Tuberculosis co-infection impacts T-cell activation markers but not the numbers subset of regulatory T-cells in HIV-1 infected patients

et al. 2013

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“…To determine whether regulatory CD4+ T cell (CD4+ Treg) frequencies differed between TB-IRIS and non-TB-IRIS patients we employed surface staining to enumerate CD25+CD127lo CD4+ T cells [9–11]. CD4+ Treg frequencies were similar in the two groups prior to ART initiation (p=0.72; Fig 2D).…”

Section: Resultsmentioning

confidence: 99%

TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in highly immunosuppressed HIV-infected patients with TB

Haridas

Pean

Jasenosky

et al. 2015

Aids

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Objective To investigate the impact of tuberculosis (TB)-associated immune reconstitution syndrome (IRIS) upon immunological recovery and the T cell compartment after initiation of TB and antiretroviral therapy (ART). Design and methods We prospectively evaluated T cell immunophenotypes by flow cytometry and cytokines by Luminex assays in a subset (n=154) of highly immunosuppressed HIV+ patients with TB from the CAMELIA randomized clinical trial. We compared findings from patients who developed TB-IRIS to findings from patients who did not develop TB-IRIS. Data were evaluated with mixed effect linear regression, Kaplan-Meier estimates, and Wilcoxon rank sum tests, and q-values were calculated to control for multiple comparisons. Results Development of TB-IRIS was associated with significantly greater pre-ART frequencies of HLA-DR+CD45RO+CD4+, CCR5+CD4+, OX40+CD4+, and Fas+ effector memory (EM) CD8+ T cells, and significantly elevated levels of plasma IL-6, IL-1β, IL-8, and IL-10 and viral load. Post-ART initiation, EM CD4+ and Fas+ EM CD4+ T cell frequencies significantly expanded, and central memory (CM) CD4+ T cell frequencies significantly contracted in patients who experienced TB-IRIS. By week 34 post-TB treatment initiation, EM/CM CD4+ T cell ratios were markedly higher in TB-IRIS versus non-TB-IRIS patients. Conclusions A distinct pattern of pre-ART T cell and cytokine markers appear to poise the immune response to develop TB-IRIS. Experience of TB-IRIS is then associated with long-term remodeling of the CD4+ T cell memory compartment towards an EM-dominated phenotype. We speculate that these pre- and post-ART TB-IRIS-associated immune parameters may contribute to superior immune control of TB/HIV co-infection and better clinical outcome.

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“…) are known to be good surrogate identification strategies for Treg identification [47]. However, the most widely accepted phenotype for Tregs is the co-expression of CD4, CD25 (α-chain of the IL-2 receptor), and of FoxP3, even in HIV-infected patients [14,36,38,39,48,49].…”

Section: Discussionmentioning

confidence: 99%

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Saison

Ferry

Demaret

et al. 2014

Clinical and Experimental Immunology

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SummaryThe mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (Tregs) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4 + T cell count (> or < 500/mm 3 ). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4 + lymphocytes, including Treg subsets, and CD8 + T cells was performed. Percentages of activated CD4 + T cells, Tregs, effector Tregs and terminal effector Tregs were found to be significantly elevated in iIR. Neither the percentage of activated CD8+ T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4 + T cell count and percentage of Tregs were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4 + and CD8+ T cells, Treg percentages and very low-level viraemia. Causative interactions between Tregs and CD4 + T cells should now be explored prospectively in a large patients cohort.

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CD4+CD25+CD127− assessment as a surrogate phenotype for FOXP3+ regulatory T cells in HIV‐1 infected viremic and aviremic subjects

Cited by 27 publications

References 22 publications

HIV and Tuberculosis co-infection impacts T-cell activation markers but not the numbers subset of regulatory T-cells in HIV-1 infected patients

HIV and Tuberculosis co-infection impacts T-cell activation markers but not the numbers subset of regulatory T-cells in HIV-1 infected patients

TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in highly immunosuppressed HIV-infected patients with TB

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

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