scholarly journals SARS-CoV-2 Humoral and Cellular Immune Responses in COVID-19 Convalescent Individuals With HIV

2022 ◽  
Author(s):  
Denise Giannone ◽  
Maria Belén Vecchione ◽  
Alejandro Czernikier ◽  
Maria Laura Polo ◽  
Virginia Gonzalez Polo ◽  
...  
Keyword(s):  
T Cell ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Neutralization Capacity ◽  
Cytokines And Chemokines ◽  
Cell Counts ◽  
Hla Dr ◽  
Ifn Γ ◽  
The Impact

Abstract Background SARS-CoV-2-specific immune response features in people with HIV infection (PWH) remain to be fully elucidated. We aimed to evaluate the impact of HIV over humoral and cellular responses in COVID-19 convalescent PWH. Methods Blood samples from 29 PWH with preserved CD4+T-cell counts on ART and 29 HIV-negative (HIVneg) donors were included. SARS-CoV-2-specific IgG levels and IgG titers were determined by ELISA. Antibody neutralization capacity was evaluated against the reference B1 strain SARS-CoV-2. IFN-γ-secreting cells were detected by ELISpot using SARS-CoV-2 Spike, RBD, or Nucleocapsid protein or overlapping peptide pools. Frequency and phenotype of T, B and NK cells and levels of soluble cytokines and chemokines were assessed by flow cytometry. Results SARS-CoV-2-specific antibodies were detected on 65.5% of PWH and 79.3% of HIVneg individuals, with no differences in serum IgG levels and anti-SARS-CoV-2 neutralizing antibodies. All donors exhibited SARS-CoV-2-specific cellular immunity, including those with undetectable antibody responses. PWH showed diminished percentages of antibody-secreting cells compared to HIVneg cohort, with similar B cell proportions between groups. PWH presented an increment in T follicular helper (Tfh, CD4+CXCR5+) percentage, which negatively correlated with IgG titers. Additionally, CD4+PD1+ and CD8+HLA-DR+ cell frequencies were augmented in PWH. Moreover, PWH presented a high proportion of CD95+, CD25+, NKp46+, HLA-DR+, and CD38+/HLA-DR+ NK cells. Both groups displayed similar Tregs frequency, effector/memory, and T-helper profile for CD4TL, exhaustion and memory phenotypes for CD8TL and subtle differences in classical monocytes. Profile of circulating cytokines and chemokines was significantly different between both groups. Magnitude of IFN-γ responses to S or N proteins, and RBD was lower in PWH compared to HIVneg donors. Correlation analysis of immune and clinical parameters showed a distinct immune landscape in the PWH group. Conclusions PWH showed a distinctive immune profile although severity of COVID-19 was not exacerbated. PWH with conserved CD4+T-cell counts exerted both humoral and cellular responses against SARS-CoV-2. Even though cellular response was lower compared to HIVneg individuals, PWH achieved similar antibody responses with a high neutralization capacity. These data reinforce the impact of ART, not only in controlling HIV but also other infections.

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.

Wilms Tumor Protein-1-Derived 9-Mer Peptide Induces CD4 T-Cell Responses in an HLA-DR Restricted Manner

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4351-4351
Author(s):  
Shigeo Fuji ◽  
Julia Fischer ◽  
Markus Kapp ◽  
Thomas G Bumm ◽  
Hermann Einsele ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Class Ii ◽  
Hla Class Ii ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Hla Dr ◽  
Ifn Γ

Abstract Abstract 4351 Wilms‘ tumor protein-1 (WT1) is one of the most investigated tumor-associated antigens (TAA) in hematological malignancies. CD8 T-cell responses against several WT1-derived peptides have been characterized and are known to contribute to disease control after allogeneic hematopoietic stem cell transplantation (HSCT). Also the identification of human leukocyte antigen (HLA) class II-restricted CD4 T-cell epitopes from WT1 is a challenging task of T-cell-based cancer immunotherapy to improve the effectiveness of WT1 peptide vaccination. We found a highly immunogenic WT1 peptide composed of only 9 amino acids having the ability to induce IFN-γ secretion in CD4 T-cells in an HLA DR-restricted manner. This finding is of great interest as it was generally accepted that HLA class II binding peptides are composed of at least 12 amino acids being recognized by CD4 T-cells, whereas HLA class I binding peptides are composed of 8–11 amino acids being recognized by CD8 T-cells (Wang et al Mol. Immunol. 2002). However, both HLA class I and class II molecules bind to primary and secondary peptide anchor motifs covering the central 9–10 amino acids. Thus, considering this common structural basis for peptide binding there is a possibility that the WT1 9-mer peptide binds to HLA class II molecules, and induces CD4 T-cell responses. IFN-γ induction in response to several WT1 9-mer peptides was screened in 24 HLA-A*02:01 positive patients with acute myeloid leukemia or myelodysplastic syndrome after allogeneic HSCT. Responses to one WT1 9-mer peptide were exclusively detected in CD3+CD4+ T-cells of 2 patients after allogeneic HSCT, but not in CD3+CD4+ T-cells of their corresponding HSC donors. CD4+ T-cell responses to this WT1 9-mer peptide exhibited high levels of functional avidity, as IFN-γ induction was detected after stimulation with 100 ng peptide per mL. Peptide-induced IFN-γ production was confirmed with IFN-γ ELISPOT assays and the HLA restriction of the T-cell response was determined by HLA blocking antibodies. The reaction was significantly blocked by anti-pan HLA class II antibody (85 % reduction), but neither by pan-HLA class I nor by anti-HLA A2 antibody. To identify the subtype of HLA class II molecule, blocking assays with antibodies against HLA-DP, HLA-DR and HLA-DQ were performed. IFN-γ induction was completely abrogated by anti-HLA-DR antibody (99 % reduction) (fig 1, p value of unpaired student‘s t-test <0.0001 for the medium control vs anti-pan HLA class II antibody or anti-HLA-DR antibody, respectively). To test whether IFN-γ was exclusively induced in CD4 T cells, CD4 or CD8 T-cells were depleted from PBMC. Whereas CD8 T-cell depletion did not affect IFN-γ induction, CD4 T-cell depletion completely abrogated the WT1 9-mer peptide induced response (fig 2). CD4 T-cells responding to the WT1 9-mer peptide were indicated to be functional cytotoxic T-cells with an effector CD4 T-cell phenotype. Longitudinal analyses demonstrated the persistence and functionality of WT1 9-mer specific CD4 T-cells in PBMC of patients even at day 1368 after allogeneic HSCT. These data indicate for the first time that a TAA-derived 9-mer peptide can induce HLA class II-restricted CD4 T-cell responses. Vaccination with the characterized WT1 9-mer peptide can enhance the induction and maintenance of not only CD4 but also indirect CD8 T-cell responses. Considering that CD4 T-cells play an important role in tumor rejection, the possibility that other TAA-derived 9-mer peptides having the potential to induce CD4 T-cell responses should be explored in other settings of tumor immunology as well to improve vaccination strategies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Impact of Cirrhosis on CD4+ T Cell Counts in HIV-Seronegative Patients

2007 ◽  
Vol 44 (3) ◽  
pp. 431-437 ◽  
Author(s):  
B. H. McGovern ◽  
Y. Golan ◽  
M. Lopez ◽  
D. Pratt ◽  
A. Lawton ◽  
...  
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
The Impact

scholarly journals Cytomegalovirus antigen-specific T Cell immune response in patients with autoimmune diseases under different cytomegalovirus infection status

2021 ◽  
Author(s):  
Huimin Ma ◽  
Yuting Tan ◽  
Xiaoqing Liu ◽  
Xiaochun Shi ◽  
Wenjie Zheng ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Cd4 T Cell ◽  
Cell Immune Response ◽  
Cmv Infection ◽  
Infection Group ◽  
Cell Counts ◽  
Ifn Γ

Abstract Background: T-cell immunity is important for the control of cytomegalovirus (CMV) infection. The frequency of IFN-γ secreting T cells after stimulation with CMV-specific protein-1 (IE-1) and phosphoprotein 65 (pp65) antigen can help predict the risk of active CMV infection. Patients with autoimmune diseases have a high incidence of active CMV infection, but the CMV antigen-specific T cell immune response of this population is still blank in the world. This study aimed to use T-SPOT.CMV to investigate CMV antigen-specific T cell immune response in patients with autoimmune diseases under different CMV infection conditions.Methods: Patients with autoimmune diseases in the Peking Union Medical College Hospital from March, 2017 to October, 2020 were continuously selected. According to the definition, the subjects were divided into latent CMV infection group and active CMV infection group. T-SPOT.CMV was used to evaluate CMV antigen-specific T cell immune response under different CMV infection status, and the possible influential factors of CMV antigen-specific T cell immune response were further analyzed.Results: Fifty patients with latent CMV infection and fifty patients with active CMV infection were enrolled. After stimulated by immediate early IE-1 and pp65 antigen, the median frequency of IFN-γ secreting T cells in active CMV infection group were all significantly lower than that in latent CMV infection group (p<0.001), and in CMV disease group was significantly lower than that in latent CMV infection group (p<0.001). After stimulated by pp65, the median frequency of IFN-γ secreting T cells with CD4+ T cell counts < 200/ul was significantly lower than that of CD4+ T cell counts ≥ 200/ul (p=0.043), and those with CD8+ T cell counts < 250/ul was significantly lower than that of CD8+ T cell counts ≥ 250/ul (p=0.03). The frequency of IFN-γ secreting T cells stimulated by pp65 was significantly higher than IE-1.Conclusions: In patients with autoimmune diseases, the CMV antigen-specific T-cell immune response in patients with active CMV infection was significantly lower than that with latent CMV infection. IE-1 was considered as a more stable antigen with better effect than pp65. Lymphocyte, CD4+T cell and CD8+T cell count might affect CMV antigen-specific T cell immune response.

The impact of diabetes on CD4 recovery in persons with HIV in an urban clinic in the United States

2017 ◽  
Vol 29 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Julie A Zuniga ◽  
Kirk A Easley ◽  
Neeta Shenvi ◽  
Minh L Nguyen ◽  
Marcia Holstad
Keyword(s):  
African American ◽  
T Cell ◽  
Cell Count ◽  
African American Women ◽  
Cd4 T Cell ◽  
Cd4 Cell Count ◽  
Cell Counts ◽  
Cd4 Cell ◽  
The Impact ◽  
Cd4 T Cell Count

The purpose of this study was to exam the impact of type 2 diabetes mellitus (T2DM) on CD4 cell count trends in adults with HIV. In a longitudinal retrospective study in an urban primary care HIV clinic in the southeastern United States from 2010 to 2012, patients with HIV medical charts were audited to obtain their CD4 cell count, diabetes status, weight, and demographic information. Rates of increase of CD4 T cell count (i.e. slopes) were obtained using a linear mixed-effects model. Most of the HIV–T2DM cohort (n = 262) and HIV-only cohort (n = 2399) were African American (76%) and male (77%). The CD4 T cell counts were consistently higher in the HIV–T2DM cohort ( p < .0001). The mean rate of CD4 T cell count increase (mean ± SE) was 63 ± 9 cells/µl/year in HIV–T2DM African American women and 28 ± 7 cells/µl/year in HIV–T2DM African American men ( p = 0.003). In the multivariable slope analysis, the CD4 T cell count increase was significantly faster for HIV–T2DM African American women than for all other patients (mean difference = 30/cells/µl/year, 95% CI: 13–47; p < 0.001). Gender, race/ethnicity, and the diagnosis of diabetes influenced the recovery of CD4 cell counts.

scholarly journals Impact of Insurance Status on Outcomes in Patients with AIDS-Defining Cancers

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Jun Yang Jiang ◽  
Erin Reid
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Private Insurance ◽  
Performance Status ◽  
Insurance Coverage ◽  
Cd4 T Cell ◽  
Treatment Delays ◽  
Cell Counts ◽  
Ryan White ◽  
The Impact

Background: Mortality among people living with the human immunodeficiency virus (PLWH [HIV]) diagnosed with acquired immunodeficiency syndrome (AIDS)-defining cancers has greatly decreased with the advent of highly active antiretroviral therapy (HAART). Recent investigations exploring the impact of insurance coverage have concluded that PLWH with public insurance have greater mortality than their privately insured counterparts. One avenue to augment medical coverage is the Ryan White HIV/AIDS Program, first authorized by Congress in 1990 to provide primary care and support services to PLWH. This study sets out to elucidate whether insurance coverage and Ryan White assistance affect treatment parameters and survival rates in PLWH diagnosed with Kaposi sarcoma (KS) and non-Hodgkin lymphomas (NHL). Methods: This was a retrospective cohort study of PLWH diagnosed with KS or NHL between 2004 and 2018. Baseline characteristics including demographics, insurance coverage, Ryan White assistance, CD4+ T-cell counts, HIV viral load, HAART treatment, performance status, and disease stage were collected. Participants were classified as having private insurance, Medicare, Medicaid, or no insurance. Treatment regimens were assessed as "optimal" or "suboptimal" using the National Comprehensive Cancer Network guidelines for AIDS-related KS and lymphomas as benchmark. Hazard ratios (HR) for survival were calculated using Cox proportional hazards regression models. Results: Among 191 participants with AIDS-defining cancers, 107 had KS, and 96 had aggressive NHL. 18% had private insurance, 14% had Medicare, 46% had Medicaid, and 23% had no health insurance; 44% received Ryan White assistance. Participants with Medicare and those without Ryan White assistance were older. Those with Ryan White assistance also had better performance status (defined as having an Eastern Cooperative Oncology Group score of 0 to 2). There were no significant differences in CD4+ T-cell counts, HIV viral loads, HAART adherence, treatment delays, regimen selection, and response rates across the insurance and Ryan White groups. The median treatment delay for all participants was 20 days. In general, participants with Medicare had lower overall survival than privately insured participants (HR 2.99, 95% confidence interval [CI] 1.14-7.87, p = 0.027). Participants without Ryan White assistance also had lower overall survival (HR 2.82, 95% CI 1.49-5.35, p = 0.002) and progression-free survival (HR 2.56, 95% CI 1.47-4.44, p &lt; 0.001) than those with assistance. Other factors that influenced overall survival were age (adjusted HR 1.04 per year of age; 95% CI 1.01-1.06; p = 0.007), Hispanic ethnicity (adjusted HR 0.46 compared to Whites; 95% CI 0.24-0.91; p = 0.025), and poor performance status (adjusted HR 6.14; 95% CI 3.39-11.12; p &lt; 0.00001). Conclusions: Our study is among the first to examine the impact of insurance coverage on outcomes in AIDS-defining malignancies. We find that PLWH with Medicare and those not receiving Ryan White assistance have lower survival. These differences may be ascribed in part to discrepancies in age, performance status, and prevalence of AIDS- and non-AIDS-related comorbidities. Reassuringly, our analysis suggests Ryan White assistance, despite its coverage limitations, is not associated with increases in treatment delays or suboptimal regimens. Nevertheless, the importance of dedicated care for this population at a multidisciplinary HIV/AIDS and comprehensive cancer center should not be undervalued. Future research should focus on whether the observed differences can be more broadly replicated in the United States. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Hepatitis C Virus Affects Tuberculosis-Specific T Cells in HIV-Negative Patients

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 101 ◽  
Author(s):  
Mohamed Ahmed El-Mokhtar ◽  
Sherein G. Elgendy ◽  
Abeer Sharaf Eldin ◽  
Elham Ahmed Hassan ◽  
Ali Abdel Azeem Hasan ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cd4 T Cells ◽  
Hcv Infection ◽  
Hla Dr ◽  
Ifn Γ ◽  
The Impact

The occurrence of tuberculosis (TB) and hepatitis C virus (HCV) infections in the same patient presents a unique clinical challenge. The impact of HCV infection on the immune response to TB remains poorly investigated in TB+/HCV+ patients. This study was conducted to evaluate the impact of HCV on the T-cell-mediated immune response to TB in coinfected patients. Sixty-four patients with active TB infections were screened for coinfection with HCV. The expression of immune activation markers IFN-γ, CD38, and HLA-DR on TB-specific CD4+ T cells was evaluated by flow cytometry in TB-monoinfected patients, TB/HCV-coinfected patients, and healthy controls. IL-2, IL-4, IFN-γ, TNF-α, and IL-10 levels were measured using ELISA. The end-of-treatment response to anti-TB therapy was recorded for both patient groups. Significantly lower levels of CD4+IFN-γ+CD38+ and CD4+IFN-γ+HLA-DR+ T cells were detected in TB/HCV-coinfected patients compared to TB monoinfected patients and controls. TB+/HCV+-coinfected patients showed higher serum levels of IL-10. The baseline frequencies of TB-specific activated T-cell subsets did not predict the response to antituberculous therapy in TB+/HCV+ patients. We concluded that different subsets of TB-specific CD4+ T cells in TB/HCV-infected individuals are partially impaired in early-stage HCV infection. This was combined with increased serum IL-10 level. Such immune modulations may represent a powerful risk factor for disease progression in patients with HCV/TB coinfection.

Persistent numbers of tetramer+ CD8+ T cells, but loss of interferon-γ+ HIV-specific T cells during progression to AIDS

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2505-2511 ◽  
Author(s):  
Stefan Kostense ◽  
Kristin Vandenberghe ◽  
Jeanine Joling ◽  
Debbie Van Baarle ◽  
Nening Nanlohy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Activity ◽  
Cd8 T Cell ◽  
Interferon Γ ◽  
Cd4 T Cell ◽  
Cytotoxic T Cell ◽  
Cell Counts ◽  
Ifn Γ

Although CD8+ T cells initially suppress human immunodeficiency virus (HIV) replication, cytotoxic T-cell precursor frequencies eventually decline and fail to prevent disease progression. In a longitudinal study including 16 individuals infected with HIV-1, we studied both the number and function of HIV-specific CD8+ T cells by comparing HLA-peptide tetramer staining and peptide-induced interferon-γ (IFN-γ) production. Numbers of IFN-γ–producing T cells declined during progression to acquired immunodeficiency syndrome (AIDS), whereas the number of tetramer+ T cells in many individuals persisted at high frequencies. Loss of IFN-γ–producing T cells correlated with declining CD4+ T-cell counts, consistent with the need of CD4+ T-cell help in maintaining adequate CD8+T-cell function. These data indicate that the loss of HIV-specific CD8+ T-cell activity is not due to physical depletion, but is mainly due to progressively impaired function of HIV-specific CD8+ T cells.

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 &lt; 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.

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