scholarly journals Increased Platelet-CD4+ T Cell Aggregates Are Correlated With HIV-1 Permissiveness and CD4+ T Cell Loss

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Peng Dai ◽  
Feng-Ying Wu ◽  
Cheng Cui ◽  
Xue-Jiao Liao ◽  
Yan-Mei Jiao ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Critical Role ◽  
Cell Loss ◽  
Cd4 T Cell ◽  
Cell Aggregates ◽  
Cell Aggregate ◽  
Aggregate Formation ◽  
Cell Counts ◽  
Hiv 1

Chronic HIV-1 infection is associated with persistent inflammation, which contributes to disease progression. Platelet-T cell aggregates play a critical role in maintaining inflammation. However, the phenotypic characteristics and clinical significance of platelet-CD4+ T cell aggregates remain unclear in different HIV-infected populations. In this study, we quantified and characterized platelet-CD4+ T cell aggregates in the peripheral blood of treatment-naïve HIV-1-infected individuals (TNs), immunological responders to antiretroviral therapy (IRs), immunological non-responders to antiretroviral therapy (INRs), and healthy controls (HCs). Flow cytometry analysis and immunofluorescence microscopy showed increased platelet-CD4+ T cell aggregate formation in TNs compared to HCs during HIV-1 infection. However, the frequencies of platelet-CD4+ T cell aggregates decreased in IRs compared to TNs, but not in INRs, which have shown severe immunological dysfunction. Platelet-CD4+ T cell aggregate frequencies were positively correlated with HIV-1 viral load but negatively correlated with CD4+ T cell counts and CD4/CD8 ratios. Furthermore, we observed a higher expression of CD45RO, HIV co-receptors, HIV activation/exhaustion markers in platelet-CD4+ T cell aggregates, which was associated with HIV-1 permissiveness. High levels of caspase-1 and caspase-3, and low levels of Bcl-2 in platelet-CD4+ T cell aggregates imply the potential role in CD4+ T cell loss during HIV-1 infection. Furthermore, platelet-CD4+ T cell aggregates contained more HIV-1 gag viral protein and HIV-1 DNA than their platelet-free CD4+ T cell counterparts. The platelet-CD4+ T cell aggregate levels were positively correlated with plasma sCD163 and sCD14 levels. Our findings demonstrate that platelet-CD4+ T cell aggregate formation has typical characteristics of HIV-1 permissiveness and is related to immune activation during HIV-1 infection.

Low CD4 T-cell counts despite low levels of circulating HIV: Insights from the comparison of HIV-1 infected patients with a discordant response to antiretroviral therapy to patients with untreated advanced HIV-2 disease

2007 ◽  
Vol 125 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Adriana S. Albuquerque ◽  
Russell B. Foxall ◽  
Catarina S. Cortesão ◽  
Rui S. Soares ◽  
Manuela Doroana ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Low Levels ◽  
Hiv 1

Distribution of HIV-1 Plasma RNA Viral Load and CD4 + T-Cell Counts Among HIV-Infected Africans Evaluated for Antiretroviral Therapy

2001 ◽  
Vol 28 (1) ◽  
pp. 99-101 ◽  
Author(s):  
John N. Nkengasong ◽  
Marie-Yolande Borget ◽  
Chantal Maurice ◽  
Emmanuel Boateng ◽  
Mireille Kalou ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Plasma Rna ◽  
Hiv 1

scholarly journals Reconstitution of Peripheral T Cells by Tissue-Derived CCR4+ Central Memory Cells Following HIV-1 Antiretroviral Therapy

2016 ◽  
Vol 1 (2) ◽  
pp. 260 ◽  
Author(s):  
Yolanda D. Mahnke ◽  
Kipper Fletez-Brant ◽  
Irini Sereti ◽  
Mario Roederer
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd8 T Cells ◽  
Plasma Viral Load ◽  
Cd4 T Cell ◽  
Cell Numbers ◽  
Cell Counts ◽  
Hiv 1

Background. Highly active antiretroviral therapy induces clinical benefits to HIV-1 infected individuals, which can be striking in those with progressive disease. Improved survival and decreased incidence of opportunistic infections go hand in hand with a suppression of the plasma viral load, an increase in peripheral CD4+ T-cell counts, as well as a reduction in the activation status of both CD4+ and CD8+ T cells.Methods. We investigated T-cell dynamics during ART by polychromatic flow cytometry in total as well as in HIV-1-specific CD4+ and CD8+ T cells. We also measured gene expression by single cell transcriptomics to assess functional state.Results. The cytokine pattern of HIV-specific CD8+ T cells was not altered after ART, though their magnitude decreased significantly as the plasma viral load was suppressed to undetectable levels. Importantly, while CD4+ T cell numbers increased substantially during the first year, the population did not normalize: the increases were largely due to expansion of mucosal-derived CCR4+ CD4+ TCM; transcriptomic analysis revealed that these are not classical Th2-type cells.Conclusion. The apparent long-term normalization of CD4+ T-cell numbers following ART does not comprise a normal balance of functionally distinct cells, but results in a dramatic Th2 shift of the reconstituting immune system.

scholarly journals Distribution of HIV-1 Plasma RNA Viral Load and CD4 + T-Cell Counts Among HIV-Infected Africans Evaluated for Antiretroviral Therapy

2001 ◽  
Vol 28 (1) ◽  
pp. 99-101
Author(s):  
John N. Nkengasong ◽  
Marie-Yolande Borget ◽  
Chantal Maurice ◽  
Emmanuel Boateng ◽  
Mireille Kalou ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Plasma Rna ◽  
Hiv 1

scholarly journals Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection

AIDS ◽  
2010 ◽  
Vol 24 (12) ◽  
pp. 1867-1876 ◽  
Author(s):  
Judith J Lok ◽  
Ronald J Bosch ◽  
Constance A Benson ◽  
Ann C Collier ◽  
Gregory K Robbins ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd4 T Cell ◽  
Combination Antiretroviral Therapy ◽  
Cell Counts ◽  
Hiv 1

HIV-1–related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4+ T-cell lymphocytes

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6100-6108 ◽  
Author(s):  
Julia Bohlius ◽  
Kurt Schmidlin ◽  
François Boué ◽  
Gerd Fätkenheuer ◽  
Margaret May ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Hodgkin Lymphoma ◽  
Cd4 T Cell ◽  
Combination Antiretroviral Therapy ◽  
Cd4 Cell Count ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Hiv 1

Abstract The risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4+ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1–infected patients (median age, 36 years; 70% male; median CD4 cell count, 234 cells/μL) from 16 European cohorts were observed during 159 133 person-years; 78 patients developed HL. The incidence was 49.0 (95% confidence interval [CI], 39.3-61.2) per 100 000 person-years, and similar on cART and not on cART (P = .96). The risk of HL declined as the most recent (time-updated) CD4 count increased: the adjusted hazard ratio comparing more than 350 with less than 50 cells/μL was 0.27 (95% CI, 0.08-0.86). Sixty-one HL cases diagnosed on cART were matched to 1652 controls: during the year before diagnosis, cases lost 98 CD4 cells (95% CI, −159 to −36 cells), whereas controls gained 35 cells (95% CI, 24-46 cells; P < .0001). The incidence of HL is not reduced by cART, and patients whose CD4 cell counts decline despite suppression of HIV-1 replication on cART may harbor HL.

scholarly journals Safety of monitoring antiretroviral therapy response in HIV-1 infection using CD4+ T cell count at long-term intervals

2018 ◽  
Vol 34 (10) ◽  
Author(s):  
Ingridt Hildegard Vogler ◽  
Daniela Frizon Alfieri ◽  
Heloisa Damazio Bruna Gianjacomo ◽  
Elaine Regina Delicato de Almeida ◽  
Edna Maria Vissoci Reiche
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Hiv 1 ◽  
Cd4 T Cell Count

Abstract: The latest Brazilian guideline recommended the reduction of routine CD4+ T cell counts for the monitoring of patients with human immunodeficiency virus type 1 (HIV-1) under combination antiretroviral therapy (cART). The aim of this study was to evaluate the safety of monitoring response to cART in HIV-1 infection using routine viral load at shorter intervals and CD4+ T cell count at longer intervals. CD4+ T cell counts and HIV-1 viral load were evaluated in 1,906 HIV-1-infected patients under cART during a three-year follow-up. Patients were stratified as sustained, non-sustained and non-responders. The proportion of patients who showed a CD4+ T > 350cells/µL at study entry among those with sustained, non-sustained and non-responders to cART and who remained with values above this threshold during follow-up was 94.1%, 81.8% and 71.9%, respectively. HIV-1-infected patients who are sustained virologic responders and have initial CD4+ T cell counts > 350cells/µL showed a higher chance of maintaining the counts of these cells above this threshold during follow-up than those presenting CD4+ T ≤ 350cells/µL (OR = 39.9; 95%CI: 26.5-60.2; p < 0.001). This study showed that HIV-1-infected patients who had sustained virologic response and initial CD4+ T > 350cells/µL were more likely to maintain CD4+ T cell counts above this threshold during the next three-year follow-up. This result underscores that the evaluation of CD4+ T cell counts in longer intervals does not impair the safety of monitoring cART response when routine viral load assessment is performed in HIV-1-infected patients with sustained virologic response.

scholarly journals Prolonged Antiretroviral Therapy Preserves HIV-1-Specific CD8 T Cells with Stem Cell-Like Properties

2015 ◽  
Vol 89 (15) ◽  
pp. 7829-7840 ◽  
Author(s):  
Selena Vigano ◽  
Jordi Negron ◽  
Zhengyu Ouyang ◽  
Eric S. Rosenberg ◽  
Bruce D. Walker ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd8 T Cells ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Cellular Immune ◽  
Hiv 1

ABSTRACTHIV-1-specific CD8 T cells can influence HIV-1 disease progression during untreated HIV-1 infection, but the functional and phenotypic properties of HIV-1-specific CD8 T cells in individuals treated with suppressive antiretroviral therapy remain less well understood. Here we show that a subgroup of HIV-1-specific CD8 T cells with stem cell-like properties, termed T memory stem cells (TSCMcells), is enriched in patients receiving suppressive antiretroviral therapy compared with their levels in untreated progressors or controllers. In addition, a prolonged duration of antiretroviral therapy was associated with a progressive increase in the relative proportions of these stem cell-like HIV-1-specific CD8 T cells. Interestingly, the proportions of HIV-1-specific CD8 TSCMcells and total HIV-1-specific CD8 TSCMcells were associated with the CD4 T cell counts during treatment with antiretroviral therapy but not with CD4 T cell counts, viral loads, or immune activation parameters in untreated patients, including controllers. HIV-1-specific CD8 TSCMcells had increased abilities to secrete interleukin-2 in response to viral antigen, while secretion of gamma interferon (IFN-γ) was more limited in comparison to alternative HIV-1-specific CD8 T cell subsets; however, only proportions of IFN-γ-secreting HIV-1-specific CD8 TSCMcells were associated with CD4 T cell counts during antiretroviral therapy. Together, these data suggest that HIV-1-specific CD8 TSCMcells represent a long-lasting component of the cellular immune response to HIV-1 that persists in an antigen-independent fashion during antiretroviral therapy but seems unable to survive and expand under conditions of ongoing viral replication during untreated infection.IMPORTANCEMemory CD8 T cells that imitate the functional properties of stem cells to maintain lifelong cellular immunity have been hypothesized for many years, but only recently have such cells, termed T memory stem cells (TSCMcells), been physically identified and isolated in humans, mice, and nonhuman primates. Here, we investigated whether cellular immune responses against HIV-1 include such T memory stem cells. Our data show that HIV-1-specific CD8 T memory stem cells are detectable during all stages of HIV-1 infection but occur most visibly at times of prolonged viral antigen suppression by antiretroviral combination therapy. These cells may therefore be particularly relevant for designing antiviral immune defense strategies against the residual reservoir of HIV-1-infected cells that persists despite treatment and leads to viral rebound upon treatment discontinuation.

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