Phenotype of Memory HCV CD8+ T Cells in Chronic HCV

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Aisha Yasin ◽  
Hala Talkhan ◽  
Afaf Abd El-Aleem ◽  
Rania Abo Shady ◽  
Rania El-Kabareety ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Cd8 T Cells ◽  
Healthcare Workers ◽  
Risk Group ◽  
High Risk Group ◽  
Proliferation Index ◽  
Memory Cd8 T Cells ◽  
Specific Memory ◽  
Chronic Hcv

Abstract Background Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. After acute infection, a majority of healthy adults will develop persistent viremia. An infection with HCV activates the immune system to defend the host with a broad range of innate and adaptive immune responses. Cellular immune response shows antiviral immunity by means of virus specific CD8+ T cytotoxic lymphocytes and CD4+ T helper cells. After resolution of infection, a population of the virus-specific memory CD8+ T cells protects the host against reinfection. These subsets of memory cells differ with respect to their anatomical localization, their phenotype and their protective potential. Objectives The aim of the present study is to find out the phenotype pattern of HCV specific memory CD8+ T cells in chronic HCV patients in comparison to HCV exposed seronegative high-risk individuals. Patients and Methods This case control study included 60 individuals categorized into two main groups, (group I) included 20 chronic HCV patients and (group II= control group) included 40 HCV seronegative healthcare workers. Both groups were subjected to carboxyfluorescein diacetate succinimidyl ester (CFSE) proliferation assay in response to HCV specific peptides. Group II was divided into 2 subgroups according to proliferation index (cut-off<2) into, proliferation index +ve high-risk group (+PIHRG) (20 healthcare workers) and proliferation index -ve high-risk group (-PIHRG) (20 healthcare workers). Then flow cytometric analysis of HCV specific CD8+ T cells was done for the all subjects to determine the expression of CD127, CCR7, CD45RO and CD45RA on both proliferating and non-proliferating fractions of cells. Results We found that expression of CD45RA was significantly increased and CCR7 was significantly decreased on HCV CD8+ T cells in the chronic HCV group than in the high risk groups in response to different HCV peptides. Conclusion During persistent viremia in chronic HCV infection subthreshold signal levels established by HCV different proteins provide anergy of virus specific memory CD8+ T cells that are unable to differentiate into full effector cells upon a possible reencounter with the antigen. So, chronic HCV patients in our study showed predominance of less differentiated effector memory phenotype (CD45RA+, CCR7-) in peripheral blood in comparison to HCV exposed seronegative high-risk individuals who don’t show overt infection.

scholarly journals Signatures of Multi-Omics Reveal Distinct Tumor Immune Microenvironment Contributing to Immunotherapy in Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziqi Huang ◽  
Baihui Li ◽  
Yan Guo ◽  
Lei Wu ◽  
Fan Kou ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Cd8 T Cells ◽  
Poor Prognosis ◽  
Molecular Subtypes ◽  
Risk Group ◽  
High Risk Group ◽  
Omics Data ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

BackgroundLung adenocarcinoma (LUAD) contains a variety of genomic and epigenomic abnormalities; the effective tumor markers related to these abnormalities need to be further explored.MethodsClustering analysis was performed based on DNA methylation (MET), DNA copy number variation (CNV), and mRNA expression data, and the differences in survival and tumor immune microenvironment (TIME) between subtypes were compared. Further, we evaluated the signatures in terms of both prognostic value and immunological characteristics.ResultsThere was a positive correlation between MET and CNV in LUAD. Integrative analysis of multi-omics data from 443 samples determined molecular subtypes, iC1 and iC2. The fractions of CD8+ T cells and activated CD4+ T cells were higher, the fraction of Tregs was lower, and the expression level of programmed death-ligand 1 (PD-L1) was higher in iC2 with a poor prognosis showing a higher TIDE score. We selected PTTG1, SLC2A1, and FAM83A as signatures of molecular subtypes to build a prognostic risk model and divided patients into high-risk group and low-risk group representing poor prognosis and good prognosis, respectively, which were validated in 180 patients with LUAD. Further, the low-risk group with lower TIDE score had more infiltrating immune cells. In 100 patients with LUAD, the high-risk group with an immunosuppressive state had a higher expression of PD-L1 and lower counts of CD8+ T cells and dendritic cells.ConclusionsThese findings demonstrated that combined multi-omics data could determine molecular subtypes with significant differences of prognosis and TIME in LUAD and suggested potent utility of the signatures to guide immunotherapy.

scholarly journals Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 155
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil Sahajpal ◽  
Vamsi Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Risk Group ◽  
High Risk Group ◽  
Free Survival ◽  
Cell Death Pathways

Lung cancer is one of the leading causes of death worldwide. Cell death pathways such as autophagy, apoptosis, and necrosis can provide useful clinical and immunological insights that can assist in the design of personalized therapeutics. In this study, variations in the expression of genes involved in cell death pathways and resulting infiltration of immune cells were explored in lung adenocarcinoma (The Cancer Genome Atlas: TCGA, lung adenocarcinoma (LUAD), 510 patients). Firstly, genes involved in autophagy (n = 34 genes), apoptosis (n = 66 genes), and necrosis (n = 32 genes) were analyzed to assess the prognostic significance in lung cancer. The significant genes were used to develop the cell death index (CDI) of 21 genes which clustered patients based on high risk (high CDI) and low risk (low CDI). The survival analysis using the Kaplan–Meier curve differentiated patients based on overall survival (40.4 months vs. 76.2 months), progression-free survival (26.2 months vs. 48.6 months), and disease-free survival (62.2 months vs. 158.2 months) (Log-rank test, p < 0.01). Cox proportional hazard model significantly associated patients in high CDI group with a higher risk of mortality (Hazard Ratio: H.R 1.75, 95% CI: 1.28–2.45, p < 0.001). Differential gene expression analysis using principal component analysis (PCA) identified genes with the highest fold change forming distinct clusters. To analyze the immune parameters in two risk groups, cytokines expression (n = 265 genes) analysis revealed the highest association of IL-15RA and IL 15 (> 1.5-fold, p < 0.01) with the high-risk group. The microenvironment cell-population (MCP)-counter algorithm identified the higher infiltration of CD8+ T cells, macrophages, and lower infiltration of neutrophils with the high-risk group. Interestingly, this group also showed a higher expression of immune checkpoint molecules CD-274 (PD-L1), CTLA-4, and T cell exhaustion genes (HAVCR2, TIGIT, LAG3, PDCD1, CXCL13, and LYN) (p < 0.01). Furthermore, functional enrichment analysis identified significant perturbations in immune pathways in the higher risk group. This study highlights the presence of an immunocompromised microenvironment indicated by the higher infiltration of cytotoxic T cells along with the presence of checkpoint molecules and T cell exhaustion genes. These patients at higher risk might be more suitable to benefit from PD-L1 blockade or other checkpoint blockade immunotherapies.

scholarly journals SARS-CoV-2 Seroprevalence in Healthcare Workers in Germany: A Follow-Up Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4540
Author(s):  
Johannes Korth ◽  
Benjamin Wilde ◽  
Sebastian Dolff ◽  
Jasmin Frisch ◽  
Michael Jahn ◽  
...  
Keyword(s):  
High Risk ◽  
Healthcare Workers ◽  
Risk Group ◽  
Close Contact ◽  
Virus Transmission ◽  
High Risk Group ◽  
Low Risk ◽  
University Hospital ◽  
Intermediate Risk ◽  
Igg Antibody

SARS-CoV-2 is a worldwide challenge for the medical sector. Healthcare workers (HCW) are a cohort vulnerable to SARS-CoV-2 infection due to frequent and close contact with COVID-19 patients. However, they are also well trained and equipped with protective gear. The SARS-CoV-2 IgG antibody status was assessed at three different time points in 450 HCW of the University Hospital Essen in Germany. HCW were stratified according to contact frequencies with COVID-19 patients in (I) a high-risk group with daily contacts with known COVID-19 patients (n = 338), (II) an intermediate-risk group with daily contacts with non-COVID-19 patients (n = 78), and (III) a low-risk group without patient contacts (n = 34). The overall seroprevalence increased from 2.2% in March–May to 4.0% in June–July to 5.1% in October–December. The SARS-CoV-2 IgG detection rate was not significantly different between the high-risk group (1.8%; 3.8%; 5.5%), the intermediate-risk group (5.1%; 6.3%; 6.1%), and the low-risk group (0%, 0%, 0%). The overall SARS-CoV-2 seroprevalence remained low in HCW in western Germany one year after the outbreak of COVID-19 in Germany, and hygiene standards seemed to be effective in preventing patient-to-staff virus transmission.

Cognate CD4 help is essential for the reactivation and expansion of CD8 memory T cells directed against the hematopoietic cell–specific dominant minor histocompatibility antigen, H60

Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4273-4280 ◽  
Author(s):  
Su Jeong Ryu ◽  
Kyung Min Jung ◽  
Hyun Seung Yoo ◽  
Tae Woo Kim ◽  
Sol Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Primary Response ◽  
Hematopoietic Cell ◽  
Secondary Response ◽  
Memory Cd8 T Cells ◽  
Specific Memory ◽  
Cd4 Help ◽  
Different Response

AbstractIn contrast to previous notions of the help-independency of memory CD8 T cells during secondary expansion, here we show that CD4 help is indispensable for the re-expansion of once-helped memory CD8 T cells, using a hematopoietic cell–specific dominant minor histocompatibility (H) antigen, H60, as a model antigen. H60-specific memory CD8 T cells generated during a helped primary response vigorously expanded only when rechallenged under helped conditions. The help requirement for an optimal secondary response was confirmed by a reduction in peak size by CD4 depletion, and was reproduced after skin transplantation. Helpless conditions or noncognate separate help during the secondary response resulted in a significant reduction in the peak size and different response kinetics. Providing CD4 help again during a tertiary challenge restored robust memory expansion; however, the repeated deprivation of help further reduced clonal expansion. Adoptively transferred memory CD8 T cells did not proliferate in CD40L−/− hosts. In the CD40−/− hosts, marginal memory expansion was detected after priming with male H60 cells but was completely abolished by priming with peptide-loaded CD40−/− cells, suggesting the essential role of CD40 and CD40L in memory responses. These results provide insight into the control of minor H antigen-specific CD8 T-cell responses, to maximize the graft-versus-leukemia response.

scholarly journals PD1 is expressed on exhausted T cells as well as virus specific memory CD8+ T cells in the bone marrow of myeloma patients

Oncotarget ◽  
2018 ◽  
Vol 9 (62) ◽  
pp. 32024-32035 ◽  
Author(s):  
Anne-Marit Sponaas ◽  
Rui Yang ◽  
Even Holth Rustad ◽  
Therese Standal ◽  
Aud Solvang Thoresen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Cd8 T Cells ◽  
Memory Cd8 T Cells ◽  
Specific Memory

scholarly journals The route of priming influences the ability of respiratory virus–specific memory CD8+ T cells to be activated by residual antigen

2010 ◽  
Vol 207 (6) ◽  
pp. 1153-1160 ◽  
Author(s):  
Shiki Takamura ◽  
Alan D. Roberts ◽  
Dawn M. Jelley-Gibbs ◽  
Susan T. Wittmer ◽  
Jacob E. Kohlmeier ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Cd8 T Cells ◽  
Respiratory Virus ◽  
Virus Infections ◽  
Memory Cd8 T Cells ◽  
Virus Clearance ◽  
Specific Memory ◽  
Respiratory Virus Infections ◽  
Lung Airways

After respiratory virus infections, memory CD8+ T cells are maintained in the lung airways by a process of continual recruitment. Previous studies have suggested that this process is controlled, at least in the initial weeks after virus clearance, by residual antigen in the lung-draining mediastinal lymph nodes (MLNs). We used mouse models of influenza and parainfluenza virus infection to show that intranasally (i.n.) primed memory CD8+ T cells possess a unique ability to be reactivated by residual antigen in the MLN compared with intraperitoneally (i.p.) primed CD8+ T cells, resulting in the preferential recruitment of i.n.-primed memory CD8+ T cells to the lung airways. Furthermore, we demonstrate that the inability of i.p.-primed memory CD8+ T cells to access residual antigen can be corrected by a subsequent i.n. virus infection. Thus, two independent factors, initial CD8+ T cell priming in the MLN and prolonged presentation of residual antigen in the MLN, are required to maintain large numbers of antigen-specific memory CD8+ T cells in the lung airways.

scholarly journals Requirement of Mature Dendritic Cells for Efficient Activation of Influenza A-Specific Memory CD8+T Cells

2000 ◽  
Vol 165 (3) ◽  
pp. 1182-1190 ◽  
Author(s):  
Marie Larsson ◽  
Davorka Messmer ◽  
Selin Somersan ◽  
Jean-François Fonteneau ◽  
Sean M. Donahoe ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Influenza A ◽  
Memory Cd8 T Cells ◽  
Specific Memory
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