scholarly journals Analysis of the Characteristics of TIGIT-Expressing CD3−CD56+NK Cells in Controlling Different Stages of HIV-1 Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Zhang ◽  
Xiaofan Lu ◽  
Allen Ka Loon Cheung ◽  
Qiuyue Zhang ◽  
Zhiying Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
Chronic Infection ◽  
Acute Infection ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Healthy Donors ◽  
Tnf Α ◽  
Ifn Γ ◽  
Hiv 1

TIGIT expression on natural killer (NK) cells is associated with dysfunction during chronic HIV infection, but the phenotype and biological functions of these cells in the context of acute HIV-1 infection remain poorly understood. Here, 19 acutely infected HIV-1 patients traced at first, third and twelfth month, and age-matched patients with chronic HIV-1 infection were enrolled to investigate the phenotype and functions of TIGIT expression on NK cells. We found that TIGIT-expressing NK cells did not increase in frequency in the first, third and twelfth month of infection until chronic HIV-1 infection lasted over 2 years. The number of TIGIT+NK cells in acute infection was positively associated with HIV-1 viral load (r = 0.53, P = 0.0009). CD96 was significantly upregulated on NK cells after acute infection for 1 month and in chronic infection over 2 years, while CD226 was downregulated in chronic infection over 2 years. Further, at different stages of infection, CD96−CD226+ cells diminished among total NK cells, TIGIT+NK and TIGIT−NK cells, while CD96+CD226− cells expanded. Reduced CD96−CD226+ cells and elevated CD96+CD226− cells among NK cells especially TIGIT−NK cells, had opposite associations with viral load in the first month of infection, as well as CD4 T-cell counts in including the twelfth month and more than 2 years of chronic infection. In both HIV-1-infected individuals and healthy donors, TIGIT was predominantly expressed in NKG2A−NKG2C+NK cells, with a significantly higher proportion than in NKG2A+NKG2C−NK cells. Moreover, the frequencies of TIGIT+NK cells were positively associated with the frequencies of NKG2A−NKG2C+NK cells in acute infection (r = 0.62, P < 0.0001), chronic infection (r = 0.37, P = 0.023) and healthy donors (r = 0.36, P = 0.020). Enhanced early activation and coexpression of CD38 and HLA-DR in TIGIT+NK cells were detected compared to TIGIT−NK cells, both of which were inversely associated with the decrease in CD4 T-cell counts in both acute and chronic HIV-1 infection. The ability of TIGIT+NK cells to produce TNF-α, IFN-γ and CD107a degranulation substance were consistently weaker than that of TIGIT−NK cells in both acute and chronic infection. Moreover, the functionalities of TIGIT+NK cells were lower than those of TIGIT−NK cells, except for TNF-α−CD107a+IFN-γ−NK cells. These findings highlight the phenotype and functional characteristics of TIGIT-expressing NK cells which have poor capabilities in inhibiting HIV-1 replication and maintaining CD4 T-cell counts.

Feasibility of a Stem Cell Gene Therapy Approach with Nonmyeloablative Conditioning in Patients with HIV-1 Infection.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 412-412
Author(s):  
Gian-Paolo Rizzardi ◽  
Silvia Nozza ◽  
Lucia Turchetto ◽  
Alexandre Harari ◽  
Giuseppe Tambussi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Cd34 Cells ◽  
Ifn Γ ◽  
Cell Gene ◽  
Stem Cell Gene ◽  
Hiv 1

Abstract Several reasons warrant the development of innovative therapeutic strategies for HIV/AIDS. These include the inability of highly active antiretroviral therapy (HAART) to eradicate the virus, the HAART-induced severe long-term toxicity occurring in patients, the development of HAART-resistant HIV-1 strains in the host, and the lack of an efficacious vaccine. Genetic engineering of hematopoietic stem cells (HSC) combined with nonmyeloablative conditioning proved safety and efficacy in the treatment of adenosine deaminase-deficient severe combined immunodeficiency. The feasibility of such an approach in HIV-1 infection remains, however, to be determined. In an open-label prospective trial, 18 patients with HIV-1 infection (mean±SE age 35.7±1.2, range 18.9–40; HAART since at least 3 months; CD4+ T cell counts >200/μl) have been enrolled in a HSC retroviral vector gene therapy trial using RevM10 and polAS as anti-HIV genes. Nine patients received fresh transduced CD34+ cells and all study treatments, including CD34+ cell mobilisation with G-CSF (10 μg/kg/day for 5 days), CD34+ cell collection through aphaeresis, and nonmyeloablative conditioning (1.8 g/m2 cyclophosphamide [CY]), while 9 did not undergo all study phases. All patients have been followed-up for at least 48 weeks. Mean±SE baseline CD4+ T cell counts were 577±42, while plasma HIV-1 RNA levels (VL) were below the limit of detection (80 copies/ml) of the assay (Nasba Organon) in 9 out of 18 patients. CD34+ cells were efficiently mobilized and collected from patients with HIV-1 infection, achieving 4.42±0.64 x 106 CD34+ cells/kg after purification (CliniMACS, Miltenyi Biotec), and 3.93±1.2 x 106 viable CD34+ cells/kg in the infusion product, 30% of which were transduced CD34+ cells. It is worth noting that 1) effective VL suppression significantly increased the yields of mobilization, purification and transduction processes, and 2) peripheral blood CD34+ cell counts before aphaeresis (mean, 72 cells/μl) predicted the number of viable CD34+ cells infused (β 0.722, 95% CI 0.007–0.092, P=0.028, regression analysis), and a cut-off value >30 CD34+ cells/μl predicted the success of all procedures (P=0.018, χ2 analysis, Fisher’s exact test). Gene marking levels, predicted by the number of transduced cells infused, were detectable in all patients, though they significantly decreased over time. CY conditioning caused a marked decrease in CD4+ T cell counts, restored over long-term follow-up. This recovery correlated with levels of CD4+ TCR-rearrangement excision circles and CD4+CD45RA+CCR7+ naïve T cells, indicating thymus regeneration capacity in >30-year-old patients with HIV-1 infection. Importantly, CMV-specific IL-2- and IFN- γ-secreting CD4+CD69+ T cells were able to expand while no clinically relevant CMV reactivation occurred; moreover, proportions of IL-2, IL-2/IFN- γ, and IFN-γ-secreting HSV, TT, and EBV-specific CD4+ T cells were not altered by CY over time. These data indicate that effective stem cell gene transfer is feasible in patients with HIV-1 infection, and suggest the use of non-lymphocyte-toxic conditioning regimen, such as busulfan.

scholarly journals Natural Killer Cell Function Is Well Preserved in Asymptomatic Human Immunodeficiency Virus Type 2 (HIV-2) Infection but Similar to That of HIV-1 Infection When CD4 T-Cell Counts Fall

2006 ◽  
Vol 80 (5) ◽  
pp. 2529-2538 ◽  
Author(s):  
Samuel Victor Nuvor ◽  
Marianne van der Sande ◽  
Sarah Rowland-Jones ◽  
Hilton Whittle ◽  
Assan Jaye
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Human Immunodeficiency Virus Type ◽  
Nk Cell ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Hiv 1

ABSTRACT Natural killer (NK) cells are potent effectors of natural immunity and their activity prevents human immunodeficiency virus type 1 (HIV-1) viral entry and viral replication. We sought to determine whether NK immune responses are associated with different clinical course of HIV-1 and HIV-2 infections. A cross-sectional analysis of NK cell responses was undertaken in 30 HIV-1 and 30 HIV-2 subjects in each of three categories of CD4+-T-cell counts (>500, 200 to 500, and <200 cells/μl) and in 50 HIV-uninfected control subjects. Lytic activity and gamma interferon (IFN-γ) secretion were measured by chromium release and enzyme-linked immunospot assays, respectively. Flow cytometry was used to assess intracellular cytokines and chemokines. Levels of NK cytotoxicity were significantly higher in HIV-2 than in HIV-1 infections in subjects with high CD4+-T-cell counts and were similar to that of the healthy controls. In these HIV-2 subjects, cytolytic activity was positively correlated to NK cell count and inversely related to plasma viremia. Levels of intracellular MIP-1β, RANTES, tumor necrosis factor alpha, and IFN-γ produced by NK CD56bright cells were significantly higher in HIV-2- than HIV-1-infected subjects with high CD4+-T-cell counts but fell to similar levels as CD4 counts dropped. The data suggest efficient cytolytic and chemokine-suppressive activity of NK cells early in HIV-2 infection, which is associated with high CD4+ T-cell counts. Enhancement of these functions may be important in immune-based therapy to control HIV disease.

NK cells of HIV-1-infected patients with poor CD4 + T-cell reconstitution despite suppressive HAART show reduced IFN-γ production and high frequency of autoreactive CD56 bright cells

2017 ◽  
Vol 190 ◽  
pp. 185-193 ◽  
Author(s):  
Erica Giuliani ◽  
Lia Vassena ◽  
Silvia Di Cesare ◽  
Vincenzo Malagnino ◽  
Maria Giovanna Desimio ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
High Frequency ◽  
Cd4 T Cell ◽  
T Cell Reconstitution ◽  
Ifn Γ ◽  
Hiv 1

scholarly journals Association of -308 TNF-alpha promoter polymorphism with viral load and CD4 T-helper cell apoptosis in HIV-1 infected black South Africans

2012 ◽  
Vol 13 (2) ◽  
Author(s):  
Shivona Gounden ◽  
Devapregasan Moodley ◽  
Anil Chuturgoon ◽  
Leshern Karamchand ◽  
Halima Dawood
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Cell Apoptosis ◽  
Promoter Polymorphism ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Hiv Progression ◽  
Increased Risk ◽  
Tnf Α ◽  
Hiv 1

Objective. To determine whether the -308 TNF-α promoter polymorphism is associated with markers of HIV progression in the South African population. Methods. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the -308 TNF-α polymorphism in 75 patients and 76 healthy controls. Serum TNF-α concentrations were measured using ELISA in each cohort. CD4+ T cell apoptosis and HIV-1 RNA viral load were determined using Annexin-V-FITC assay and Nuclisens Easy Q HIV-1 assay respectively. CD4 + T cell counts were measured flow cytometrically. Results. The frequency of -308 G allele was similar in the HIV-1 and control cohorts. The -308GG genotype was associated with lower TNF-α concentrations and markers of increased HIV progression indicated by higher TH lymphocyte apoptosis, lower TH lymphocyte count and higher plasma viral load, irrespective of treatment. Conclusion. The presence of the TNF-α -308 G allele in HIV-1 patients may be associated with increased risk of HIV-1 progression. Further research is required to investigate the nature of this association. S Afr J HIV Med 2012;13(2):72-77.

The Effect of Antiretroviral Therapy on IL-6, IL-1β, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients

2020 ◽  
Vol 18 (5) ◽  
pp. 354-361
Author(s):  
Gülay Okay ◽  
Meliha Meric Koc ◽  
Eray Metin Guler ◽  
Ayşegül Yabaci ◽  
Abdürrahim Kocyigit ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Cell Count ◽  
Cd4 T Cell ◽  
Positive Correlation ◽  
Hiv Rna ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Cd4 T Cell Count

Background: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). Objectives: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. Methods: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. Results: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). Conclusions: Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.

scholarly journals Relaxation of Adaptive Evolution during the HIV-1 Infection Owing to Reduction of CD4+ T Cell Counts

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e39776 ◽  
Author(s):  
Élcio Leal ◽  
Jorge Casseb ◽  
Michael Hendry ◽  
Michael P. Busch ◽  
Ricardo Sobhie Diaz
Keyword(s):  
T Cell ◽  
Adaptive Evolution ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Hiv 1

scholarly journals P16-53. Distinct subsets of memory T lymphocytes from HIV-1-infected subjects secrete IFN-γ and IL-2 in response to novel CD4+ T-cell HIV-1 epitopes

Retrovirology ◽  
2009 ◽  
Vol 6 (S3) ◽  
Author(s):  
S Fonseca ◽  
A Coutinho-Silva ◽  
D Rodrigues ◽  
L Marti ◽  
C Moreira-Filho ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cd4 T Cell ◽  
Ifn Γ ◽  
Memory T Lymphocytes ◽  
Hiv 1

scholarly journals Vδ1 T lymphocytes producing IFN-γ and IL-17 are expanded in HIV-1–infected patients and respond to Candida albicans

Blood ◽  
2009 ◽  
Vol 113 (26) ◽  
pp. 6611-6618 ◽  
Author(s):  
Daniela Fenoglio ◽  
Alessandro Poggi ◽  
Silvia Catellani ◽  
Florinda Battaglia ◽  
Alessandra Ferrera ◽  
...  
Keyword(s):  
T Cells ◽  
Candida Albicans ◽  
T Cell ◽  
T Lymphocytes ◽  
Receptor Expression ◽  
Interleukin 17 ◽  
Γδ T Cell ◽  
Healthy Donors ◽  
Ifn Γ ◽  
Hiv 1

AbstractIn early HIV-1 infection, Vδ1 T lymphocytes are increased in peripheral blood and this is related to chemokine receptor expression, chemokine response, and recirculation. Herein we show that, at variance with healthy donors, in HIV-1–infected patients ex vivo–isolated Vδ1 T cells display cytoplasmic interferon-γ (IFN-γ). Interestingly, these cells coexpress cytoplasmic interleukin-17 (IL-17), and bear the CD27 surface marker of the memory T-cell subset. Vδ1 T cells, isolated from either patients or healthy donors, can proliferate and produce IFN-γ and IL-17 in response to Candida albicans in vitro, whereas Vδ2 T cells respond with proliferation and IFN-γ/IL-17 production to mycobacterial or phosphate antigens. These IFN-γ/IL-17 double-producer γδ T cells express the Th17 RORC and the Th1 TXB21 transcription factors and bear the CCR7 homing receptor and the CD161 molecule that are involved in γδ T-cell transendothelial migration. Moreover, Vδ1 T cells responding to C albicans express the chemokine receptors CCR4 and CCR6. This specifically equipped circulating memory γδ T-cell population might play an important role in the control of HIV-1 spreading and in the defense against opportunistic infections, possibly contributing to compensate for the impairment of CD4+ T cells.

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