Different Immunological Phenotypes Associated with Preserved CD4+ T Cell Counts in HIV-Infected Controllers and Viremic Long Term Non-Progressors

Gaardbo, Julie C.; Hartling, Hans J.; Ronit, Andreas; Thorsteinsson, Kristina; Madsen, Hans O.; Springborg, Karoline; Gjerdrum, Lise Mette Rahbek; Birch, Carsten; Laye, Matthew J.; Ullum, Henrik; Andersen, Anita Sylvest; Nielsen, Susanne Dam

doi:10.1371/journal.pone.0063744

Cited by 17 publications

(12 citation statements)

References 42 publications

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“…Gating strategies have been published elsewhere. 31,32 In brief, 100 mL of fresh EDTA blood was incubated with fluorescent dye-conjugated monoclonal antibodies according to the manufacturer's instructions. Monoclonal antibodies used to determine lymphocyte subsets were isotype control IgG1/IgG2a phycoerythrin (PE), IgG1 peridinin chlorophyll proteins-cyanine (PerCP-Cy5.5), IgG1/IgM fluorescein isothiocyanate (FITC), IgG1/IgG2b allophycocyanin (APC), IgG1 PE-Cy7, IgG1 APC-H7, CCR7-PE, CD161-PE, CD28-PE, Foxp3-PE, CD8-PerCP-Cy5.5, CD25-PerCP-Cy5.5, CD3-FITC, CD127-FITC, CD57-FITC, HLA-DR-APC, CD45RA-APC, CD95-FITC, CD27-PE-Cy7, CD38-PE-Cy7, CD69-PE-Cy7, and CD4-APC-H7, all purchased from BD.…”

Section: Flow Cytometrymentioning

confidence: 99%

Increased Tryptophan Catabolism Is Associated With Increased Frequency of CD161+Tc17/MAIT Cells and Lower CD4+ T-Cell Count in HIV-1 Infected Patients on cART After 2 Years of Follow-Up

Gaardbo

Trøsied

Stiksrud

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Section: Flow Cytometrymentioning

confidence: 99%

Increased Tryptophan Catabolism Is Associated With Increased Frequency of CD161+Tc17/MAIT Cells and Lower CD4+ T-Cell Count in HIV-1 Infected Patients on cART After 2 Years of Follow-Up

Gaardbo

Trøsied

Stiksrud

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Lymphocyte subsets are given as the proportion (%) of the cell population concerned (CD4+ T cells or CD8+ T cells, respectively) as well as absolute CD4+ and CD8+ T-cell counts. T-cell subsets determined were RTE (CD45RA+ CD31+), naive cells (CD45RA+ CD27+ CCR7+), central memory cells (CM) (CD45RA-CD27+ CCR7+), effector memory cells (EM) (CD45RA-CD27+ CCR7-), late-differentiated cells (CD45RA+ CD27-CCR7-), apoptotic cells (CD28-CD95+), immune-activated cells (CD38+), and IL-7Ra expressing cells (CD127+) (16,17). Furthermore, to characterize the receptor density of Il-7Ra on each IL-7Ra+ T cell, we analyzed the median fluorescence intensity (MFI) of IL-7Ra on IL-7Ra+ T cells.…”

Section: Flow Cytometrymentioning

confidence: 99%

“…In contrast, memory T cells have been exposed to their cognate antigen and become specific for this. Destruction of T cells can be assessed by determination of apoptotic T cells (16,17). An essential driver of proliferation and de novo production of T cells is Interleukin-7 (IL-7).…”

mentioning

confidence: 99%

T‐cell homeostasis in chronic HCV‐infected patients treated with interferon and ribavirin or an interferon‐free regimen

Hartling

Birch

Gaardbo

et al. 2015

APMIS

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Direct-acting antiviral has replaced pegylated interferon-α and ribavirin-based treatment in the treatment of chronic hepatitis C virus (HCV) infection. While interferon-α is immune modulating and causes lymphopenia, interferon-free regimens seem to be well-tolerated. This study aimed to compare T-cell homeostasis before, during, and after HCV treatment with or without interferon-α in patients with chronic HCV infection. A total of 20 patients with chronic HCV infection were treated with pegylated interferon-α and ribavirin, and six patients were treated with an interferon-free regimen. All patients were treated for a minimum of 12 weeks. Interferon-α treatment caused an increase in the density of the receptor for IL-7 (IL-7Rα) during treatment, while interferon-free regimens caused a decrease in IL-7Rα density. After a sustained viral response, proportions of IL-7Rα+ T cells and IL-7Rα density decreased compared to prior treatment values. Finally, a proportion of CD8+ effector memory was lower while proportion of apoptotic T cells was higher after sustained virologic response compared to prior treatment. Despite lymphopenia during interferon, alterations in T-cell homeostasis during treatment were relatively similar in patients receiving interferon-based treatment and in patients receiving interferon-free treatment, and alterations during and after treatment seem to illustrate a reduced need for high levels of T cells aimed at controlling infection.

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“…An additional feature of SIV infection of natural hosts is low peripheral immune activation (10). However, there are conflicting reports with respect to levels of immune activation in VNPs (11)(12)(13)(14). Also, preservation of CD4+ T cell counts over extended periods of infection in the face of ongoing viral replication presents an opportunity to evaluate T cell homeostasis and perturbations in T cell dynamics within these individuals compared to those with typical progression.…”

Section: Introductionmentioning

confidence: 99%

Delineation of Homeostatic Immune Signatures Defining Viremic Non-progression in HIV-1 Infection

et al. 2020

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Viremic non-progressors (VNPs), a distinct group of HIV-1-infected individuals, exhibit no signs of disease progression and maintain persistently elevated CD4+ T cell counts for several years despite high viral replication. Comprehensive characterization of homeostatic cellular immune signatures in VNPs can provide unique insights into mechanisms responsible for coping with viral pathogenesis as well as identifying strategies for immune restoration under clinically relevant settings such as antiretroviral therapy (ART) failure. We report a novel homeostatic signature in VNPs, the preservation of the central memory CD4+ T cell (CD4+ T CM) compartment. In addition, CD4+ T CM preservation was supported by ongoing interleukin-7 (IL-7)-mediated thymic repopulation of naive CD4+ T cells leading to intact CD4+ T cell homeostasis in VNPs. Regulatory T cell (Treg) expansion was found to be a function of preserved CD4+ T cell count and CD4+ T cell activation independent of disease status. However, in light of continual depletion of CD4+ T cell count in progressors but not in VNPs, Tregs appear to be involved in lack of disease progression despite high viremia. In addition to these homeostatic mechanisms resisting CD4+ T cell depletion in VNPs, a relative diminution of terminally differentiated effector subset was observed exclusively in these individuals that might ameliorate consequences of high viral replication. VNPs also shared signatures of impaired CD8+ T cell cytotoxic function with progressors evidenced by increased exhaustion (PD-1 upregulation) and CD127 (IL-7Rα) downregulation contributing to persistent viremia. Thus, the homeostatic immune signatures reported in our study suggest a complex multifactorial mechanism accounting for non-progression in VNPs.

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Different Immunological Phenotypes Associated with Preserved CD4+ T Cell Counts in HIV-Infected Controllers and Viremic Long Term Non-Progressors

Cited by 17 publications

References 42 publications

Increased Tryptophan Catabolism Is Associated With Increased Frequency of CD161+Tc17/MAIT Cells and Lower CD4+ T-Cell Count in HIV-1 Infected Patients on cART After 2 Years of Follow-Up

Increased Tryptophan Catabolism Is Associated With Increased Frequency of CD161+Tc17/MAIT Cells and Lower CD4+ T-Cell Count in HIV-1 Infected Patients on cART After 2 Years of Follow-Up

T‐cell homeostasis in chronic HCV‐infected patients treated with interferon and ribavirin or an interferon‐free regimen

Delineation of Homeostatic Immune Signatures Defining Viremic Non-progression in HIV-1 Infection

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