CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides

Barathan, Muttiah; Rosmawati, Mohamed; Vadivelu, Jamuna; Chang, Li; Vignesh, Ramachandran; Krishnan, Jayalakshmi; Panneer, Sigamani; Saeidi, Alireza; Ram, M. Ravishankar; Vijayakumar, V.; Larsson, Marie; Shankar, Esaki M.

doi:10.1016/j.cellimm.2016.12.002

Cited by 23 publications

(16 citation statements)

References 49 publications

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“…Of particularly importance, screening of a large variety of ICs would provide guidance for evaluating the hierarchy of ICs expressed on virus‐specific T cells. Indeed, an apparent domination of PD‐1 was observed on both HBV‐specific CD8 + and CD4 + T cells . For HBV‐specific CD8 + T cells, PD‐1 domination was followed by KLRG1, 2B4, and CD160 .…”

Section: The Regulation Of Multiple Ics During Chronic Hbv and Hcv Inmentioning

confidence: 72%

“…Indeed, an apparent domination of PD-1 was observed on both HBV-specific CD8 + and CD4 + T cells. 28,86,88 For HBV-specific CD8 + T cells, PD-1 domination was followed by KLRG1, 2B4, and CD160. 11 Likewise, an obvious domination of PD-1 was also observed in a cohort of chronic HCV patients, followed by 2B4, KLRG1, and CD160.…”

Section: Hiv Priming Of Naïve T Cells With Hiv-pulsed Dcs Inducedmentioning

confidence: 99%

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Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

Hakim

Rahmadika

Jariah

2019

Reviews in Medical Virology

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Summary The function of T cells is tightly controlled by positive and negative regulations to ensure both successful pathogen elimination and limitation of immune‐mediated pathology. One of the mechanisms to negatively regulate the magnitude and duration of effector T cells is the expression of inhibitory checkpoint molecules (ICs) on the surface membrane of T cells. During acute viral infections, expression of these molecules is upregulated to limit the effector functions following T‐cell activation. The expression is subsequently downregulated following viral clearance. In contrast, these molecules are continuously expressed in virus‐specific T cells found in persistently infected patients, including cases of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV). The continuously high expression of ICs is responsible for the dysfunctional states of HBV‐ and HCV‐specific T cells in chronic phases, known as T‐cell exhaustion. Hence, understanding the regulation of their expression is essential to give insight into pathogenesis as well as the development of effective immune‐based antiviral therapies. This review discusses recent updated research on expression of ICs during acute and chronic phases of HBV and HCV infections as well as during the clinical course of antiviral therapy.

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Section: The Regulation Of Multiple Ics During Chronic Hbv and Hcv Inmentioning

confidence: 72%

Section: Hiv Priming Of Naïve T Cells With Hiv-pulsed Dcs Inducedmentioning

confidence: 99%

Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

Hakim

Rahmadika

Jariah

2019

Reviews in Medical Virology

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“…Immune exhaustion in chronic viral infections is most likely caused by alterations in many cell signaling pathways other than the upregulation of the PD-1/PD-L1 pathway. For example, infection with HIV or the hepatitis C virus increases the expression of a number of negative co-stimulatory molecules, including lymphocyte activation gene-3 (LAG-3), CD160, cytolytic T-lymphocyte antigen-4 (CTLA-4), T-cell immunoglobulin mucin-containing domain-3 (TIM-3), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) [32,33]. Moreover, immune exhaustion might be related to mitochondrial dysfunction in immune effector cells [34].…”

Section: Discussionmentioning

confidence: 99%

ThymicPeptides Reverse Immune Exhaustion in Patients with Reactivated Human Alphaherpesvirus1 Infections

Hymos

Grywalska

Klatka

et al. 2020

IJMS

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Recurrent infection with human alphaherpesvirus 1 (HHV-1) may be associated with immune exhaustion that impairs virus elimination. Thymic peptides enhance immune function and thus could overcome immune exhaustion. In this study, we investigated whether reactivation of herpes infections was associated with immune exhaustion. Moreover, we examined the impact of treatment with thymostimulin on the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on T and B lymphocytes in patients suffering from recurrent HHV-1 reactivation. We also assessed the effector function of peripheral blood mononuclear cells (PBMCs) after stimulation with thymic peptides. We enrolled 50 women with reactivated HHV-1 infections and healthy volunteers. We measured the expression of various activation and exhaustion markers on the surface of PBMCs using flow cytometry. In ex vivo experiments, we measured the secretion of inflammatory cytokines by PBMCs cultured with thymostimulin. Compared with controls, patients with reactivated HHV-1 infections had increased percentages of CD3+ co-expressing CD25, an activation marker (p < 0.001). Moreover, these patients had increased percentages of CD4+ and CD8+ cells co-expressing the inhibitory markers PD-1 and PD-L1. In cultures of PBMCs from the patients, thymostimulin increased the secretion of interferon gamma (p < 0.001) and interleukin (IL)-2 (p = 0.023), but not IL-4 or IL-10.Two-month thymostimulin therapy resulted in no reactivation of HHV-1 infection during this period and the reduction of PD-1 and PD-L1 expression on the surface of T and B lymphocytes (p < 0.001). In conclusion, reactivation of herpes infection is associated with immune exhaustion, which could be reversed by treatment with thymic peptides.

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“…T cells play a critical role in infection, cancer, and autoimmune diseases. During chronic viral infection and cancer, Ag‐specific CD8 + T cells often become dysfunctional or exhausted that serves as a barrier to successful antitumor and antiviral immunotherapy . Identifying core transcriptional signatures of dysfunctional T cells may help developing therapies against chronic infection and cancer.…”

Section: Application Of Scrna‐seq In Immunologymentioning

confidence: 99%

“…During chronic viral infection and cancer, Ag-specific CD8 + T cells often become dysfunctional or exhausted that serves as a barrier to successful antitumor and antiviral immunotherapy. [70][71][72][73] Identifying core transcriptional signatures of dysfunctional T cells may help developing therapies against chronic infection and cancer. Recently, TOX protein was found to regulate the expression of multiple inhibitory molecules including PD-1, Lag-3, and Tim-3, and determine the survival of dysfunctional/exhausted T cells using scRNA-seq.…”

Section: Application Of Scrna-seq In Cancer Infectious and Autoimmumentioning

confidence: 99%

Dissecting the human immune system with single cell RNA sequencing technology

Liu

et al. 2019

Journal of Leukocyte Biology

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Single‐cell RNA sequencing (scRNA‐seq) is a powerful new technology allowing the analysis of transcriptomes from individual cell and is ideally suited to dissect immune cell heterogeneity. ScRNA‐seq has already been applied to identify novel immune cell subsets, elaborate cellular differentiation trajectories, and elucidate immunopathogenic mechanisms. Here, we briefly discuss the recent progresses and challenges in the scRNA‐seq technology including the workflow, recent applications in immunology, and potential hurdles that need to be overcome. This review will highlight how single cell technology promotes our understanding of human immunology.

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CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides

Cited by 23 publications

References 49 publications

Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

ThymicPeptides Reverse Immune Exhaustion in Patients with Reactivated Human Alphaherpesvirus1 Infections

Dissecting the human immune system with single cell RNA sequencing technology

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