scholarly journals The Effect of Rosuvastatin on Markers of Immune Activation in Treatment-Naive Human Immunodeficiency Virus-Patients

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Robyn G. M. Weijma ◽  
Eric R. A. Vos ◽  
Jaap Ten Oever ◽  
Muriel Van Schilfgaarde ◽  
Lea M. Dijksman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Cell Activation ◽  
Immune Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Activation Markers ◽  
Cell Ratio ◽  
Immunodeficiency Virus ◽  
Treatment Naïve

Abstract Background.  Immune activation has been implicated in the excess mortality in human immunodeficiency virus (HIV)-infected patients, due to cardiovascular diseases and malignancies. Statins may modulate this immune activation. We assessed the capacity of rosuvastatin to mitigate immune activation in treatment-naive HIV-infected patients. Methods.  In a randomized double-blind placebo-controlled crossover study, we explored the effects of 8 weeks of rosuvastatin 20 mg in treatment-naive male HIV-infected patients (n = 28) on immune activation markers: neopterin, soluble Toll-like receptor (TLR)2, sTLR4, interleukin (IL)-6, IL-1Ra, IL-18, d-dimer, highly sensitive C-reactive protein, and CD38 and/or human leukocyte antigen-DR expression on T cells. Baseline data were compared with healthy male controls (n = 10). Furthermore, the effects of rosuvastatin on HIV-1 RNA, CD4/CD8 T-cell count, and low-density lipoprotein cholesterol were examined and side effects were registered. Results.  T-cell activation levels were higher in patients than in controls. Patients had higher levels of circulating IL-18, sTLR2, and neopterin (all P < .01). Twenty patients completed the study. Rosuvastatin increased the CD4/CD8 T-cell ratio (P = .02). No effect on other markers was found. Conclusions.  Patients infected with HIV had higher levels of circulating neopterin, IL-18, sTLR2, and T-cell activation markers. Rosuvastatin had a small but significant positive effect on CD4/CD8 T-cell ratio, but no influence on other markers of T-cell activation and innate immunity was identified (The Netherlands National Trial Register [NTR] NTR 2349, http://www.trialregister.nl/trialreg/index.asp).

scholarly journals Human Immunodeficiency Virus-Specific Circulating CD8 T Lymphocytes Have Down-Modulated CD3ζ and CD28, Key Signaling Molecules for T-Cell Activation

2000 ◽  
Vol 74 (16) ◽  
pp. 7320-7330 ◽  
Author(s):  
Linda A. Trimble ◽  
Premlata Shankar ◽  
Mark Patterson ◽  
Johanna P. Daily ◽  
Judy Lieberman
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Cd8 T Lymphocytes ◽  
Immunodeficiency Virus

ABSTRACT Although human immunodeficiency virus (HIV)-infected subjects without AIDS have a high frequency of HIV-specific CD8 T lymphocytes, cellular immunity is unable to control infection. Freshly isolated lymphocytes often do not lyse HIV-infected targets in 4-h cytotoxicity assays. A large fraction of circulating CD8 T cells from HIV-infected donors down-modulate CD3ζ, the signaling component of the T-cell receptor complex, which is reexpressed in vitro coincident with the return of cytotoxic function. To investigate further the link between CD3ζ down-modulation and possible CD8 T-cell functional defects, we used flow cytometry to characterize further the properties of the CD3ζ-down-modulated subset. HIV-specific CD8 T cells, identified by tetramer staining, are CD3ζ−. CD8 T cells with down-modulated CD3ζ also do not express the key costimulatory receptor CD28 and have the cell surface phenotype of activated or memory T cells (HLA-DR+ CD62L−). After T-cell activation, CD3ζ-down-modulated cells express the activation marker CD69 but not the high-affinity interleukin 2 (IL-2) receptor α-chain CD25 and produce gamma interferon but not IL-2. Therefore HIV-specific CD8 T cells have down-modulated key signaling molecules for T-cell activation and costimulation and require exogenous cytokine stimulation. The typical impairment of HIV-specific CD4 T helper cells, which would normally provide specific CD8 T-cell stimulation, means that in vivo CTL function in vivo is compromised in most HIV-infected individuals. In AIDS patients, the functional defect is more severe, since CD3ζ is not reexpressed even after IL-2 exposure.

scholarly journals CD8+T Cell Activation in Women Coinfected with Human Immunodeficiency Virus Type 1 and Hepatitis C Virus

2008 ◽  
Vol 197 (10) ◽  
pp. 1402-1407 ◽  
Author(s):  
Andrea Kovacs ◽  
Lena Al‐Harthi ◽  
Shawna Christensen ◽  
Wendy Mack ◽  
Mardge Cohen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Immunodeficiency Virus

scholarly journals Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion

2019 ◽  
Vol 221 (7) ◽  
pp. 1135-1145 ◽  
Author(s):  
Genevieve E Martin ◽  
Matthew Pace ◽  
Freya M Shearer ◽  
Eva Zilber ◽  
Jacob Hurst ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Hiv Dna ◽  
Art Initiation ◽  
Immunodeficiency Virus

Abstract Initiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet−Eomes− subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.

scholarly journals Sex-Based Differences in Human Immunodeficiency Virus Type 1 Reservoir Activity and Residual Immune Activation

2018 ◽  
Vol 219 (7) ◽  
pp. 1084-1094 ◽  
Author(s):  
Eileen P Scully ◽  
Monica Gandhi ◽  
Rowena Johnston ◽  
Rebecca Hoh ◽  
Ainsley Lockhart ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
T Cell Activation ◽  
Immune Activation ◽  
Cell Activation ◽  
Immunodeficiency Virus ◽  
Hiv 1

Abstract Plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in women are lower early in untreated HIV-1 infection compared with those in men, but women have higher T-cell activation and faster disease progression when adjusted for viral load. It is not known whether these sex differences persist during effective antiretroviral therapy (ART), or whether they would be relevant for the evaluation and implementation of HIV-1 cure strategies. We prospectively enrolled a cohort of reproductive-aged women and matched men on suppressive ART and measured markers of HIV-1 persistence, residual virus activity, and immune activation. The frequency of CD4+ T cells harboring HIV-1 DNA was comparable between the sexes, but there was higher cell-associated HIV-1 RNA, higher plasma HIV-1 (single copy assay), and higher T-cell activation and PD-1 expression in men compared with women. These sex-related differences in immune phenotype and HIV-1 persistence on ART have significant implications for the design and measurement of curative interventions.

scholarly journals Maintenance of Viral Suppression in Human Immunodeficiency Virus Controllers Despite Waning T-Cell Responses During Antiretroviral Therapy

2020 ◽  
Vol 222 (11) ◽  
pp. 1837-1842 ◽  
Author(s):  
Nikolaus Jilg ◽  
Pilar Garcia-Broncano ◽  
Michael Peluso ◽  
Florencia P Segal ◽  
Ronald J Bosch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
T Cell Activation ◽  
Cell Activation ◽  
T Cell Responses ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Undetectable Viremia ◽  
Hiv Controllers

Abstract AIDS Clinical Trials Group study A5308 found reduced T-cell activation and exhaustion in human immunodeficiency virus (HIV) controllers start antiretroviral therapy (ART). We further assessed HIV-specific T-cell responses and post-ART viral loads. Before ART, the 31% of participants with persistently undetectable viremia had more robust HIV-specific T-cell responses. During ART, significant decreases were observed in a broad range of T-cell responses. Eight controllers in A5308 and the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort showed no viremia above the level of quantification in the first 12 weeks after ART discontinuation. ART significantly reduced HIV-specific T-cell responses in HIV controllers but did not adversely affect controller status after ART discontinuation.

Non-mitogenic T cell activation signals are sufficient for induction of human immunodeficiency virus transcription

1991 ◽  
Vol 21 (1) ◽  
pp. 167-172 ◽  
Author(s):  
Rob A. Gruters ◽  
Sigrid A. Otto ◽  
Bert J. M. Al ◽  
Arthur J. Verhoeven ◽  
Cornelis L. Verweij ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Virus Transcription ◽  
Immunodeficiency Virus

scholarly journals Human Immunodeficiency Virus Type 1 Vpr Impairs Dendritic Cell Maturation and T-Cell Activation: Implications for Viral Immune Escape

2005 ◽  
Vol 79 (13) ◽  
pp. 7990-8003 ◽  
Author(s):  
Biswanath Majumder ◽  
Michelle L. Janket ◽  
Elizabeth A. Schafer ◽  
Keri Schaubert ◽  
Xiao-Li Huang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
T Cell Activation ◽  
Immune Evasion ◽  
Cell Activation ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Cytokine Profiling

ABSTRACT Antigen presentation and T-cell activation are dynamic processes involving signaling molecules present in both APCs and T cells. Effective APC function and T-cell activation can be compromised by viral immune evasion strategies, including those of human immunodeficiency virus type 1 (HIV-1). In this study, we determined the effects of HIV-1 Vpr on one of the initial target of the virus, dendritic cells (DC), by investigating DC maturation, cytokine profiling, and CD8-specific T-cell stimulation function followed by a second signal. Vpr impaired the expression of CD80, CD83, and CD86 at the transcriptional level without altering normal cellular transcription. Cytokine profiling indicated that the presence of Vpr inhibited production of interleukin 12 (IL-12) and upregulated IL-10, whereas IL-6 and IL-1β were unaltered. Furthermore, DC infected with HIV-1 vpr + significantly reduced the activation of antigen-specific memory and recall cytotoxic-T-lymphocyte responses. Taken together, these results indicate that HIV-1 Vpr may in part be responsible for HIV-1 immune evasion by inhibiting the maturation of costimulatory molecules and cytokines essential for immune activation.

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