Increased Expression of Cytotoxic T-Lymphocyte−Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure

Khamri, Wafa; Abeles, R.D.; Hou, Tie Zheng; Anderson, Amy E.; Elmasry, Ahmed; Triantafyllou, Evangelos; Bernsmeier, Christine; Larsen, Fin Stolze; Singanayagam, Arjuna; Kudo, Norio; Possamai, Lucia; Lebossé, Fanny; Auzinger, G.; Bernal, William; Willars, Christopher; Weston, Chris J.; Lombardi, Giovanna; Wendon, Julia; Thursz, Mark; Antoniades, Charalambos

doi:10.1053/j.gastro.2017.03.023

Cited by 43 publications

(51 citation statements)

References 47 publications

(72 reference statements)

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“…In line with previous reports [5,14,18] , the proportion of circulating CD8 + T cells in cirrhotic patients was significantly diminished compared to HV (median values: 8.99% vs 19.85% respectively; p < 0.0 0 01). Furthermore, analyses of cytolytic mediators in CD8 + T cells from patients with cirrhosis showed significantly decreased perforin expression compared to HV (median values 18.05% vs 47.53%, respectively; p = 0.049) ( Fig.…”

Section: Peripheral Cd8 + T Cells From Cirrhotic Patients Display Ansupporting

confidence: 92%

“…Although partially explored, adaptive immune defects are important drivers of immune-paresis and susceptibility to infection in liver diseases. We and others have provided evidence that impaired antimicrobial responses in ALF and alcoholic acute hepatitis (AAH) were mediated by an altered phenotype of CD4 + and CD8 + T lymphocytes characterized by elevated levels of immune checkpoints PD-1, TIM-3 and CTLA-4 [10,14] .…”

Section: Introductionmentioning

confidence: 99%

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CD8+ T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction

et al. 2019

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a b s t r a c tBackground: Cirrhosis-associated immune dysfunction (CAID) contributes to high sepsis risk in patients with chronic liver disease. Various innate and; to a lesser extent; adaptive immune dysfunctions have been described as contributors to CAID leading to immune-paresis and impaired anti-microbial response in cirrhosis. In this study, we examined the phenotype of CD8 + T cells in chronic liver disease with the aim to evaluate changes that might contribute to impaired immune responses. Methods: Sixty patients with cirrhosis were prospectively recruited for this study. CD8 + T cells from peripheral blood, ascites and liver explants were characterized using flow cytometry and immunohistochemistry, respectively. The transcriptional signature of flow-sorted HLA-DR + CD8 + T cells was performed using Nanostring TM technology. HLA-DR + CD8 + T cells interactions with PBMCs and myeloid cells were tested in vitro . Findings: Peripheral CD8 + T cells from cirrhotic patients displayed an altered phenotype characterized by high HLA-DR and TIM-3 surface expression associated with concomitant infections and disease severity, respectively. Paired peritoneal CD8 + T cells expressed more pronounced levels of HLA-DR and PD-1 compared to peripheral CD8 + T cells. HLA-DR + CD8 + T cells were enriched in cirrhotic livers compared to controls. TIM-3, CTLA-4 and PD-1 levels were highly expressed on HLA-DR + CD8 + T cells and co-expression of HLA-DR and PD1 was higher in patients with poor disease outcomes. Genes involved in cytokines production and intracellular signalling pathways were strongly down-regulated in HLA-DR + CD8 + T cells. In comparison to their HLA-DR − counterparts, HLA-DR + CD8 + T cells promoted less proliferation of PBMCs and induced phenotypic and functional dysfunctions in monocytes and neutrophils in vitro . Interpretation: In patients with cirrhosis, CD8 + T cells display a phenotypic, functional and transcriptional profile which may contribute to CAID.

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Section: Peripheral Cd8 + T Cells From Cirrhotic Patients Display Ansupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

CD8+ T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction

et al. 2019

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“…Previous studies showed that the pathogenesis of the disease is roughly classi ed into two aspects: direct damage and immune mediation [23], where cellular immune disorders may be the key to the occurrence of liver failure. In cellular immunity, T lymphocytes are the main effectors, which contain different subpopulations to complete the immune response to exert immune regulatory functions [24,25]. The occurrence of liver failure is caused by the killing effect of the cells during the process of clearing virus [3,20,26].…”

Section: Discussionmentioning

confidence: 99%

“…The data were expressed as means ± SD or medians with interquartile range. SPSS software V. 25 Table 1, among whom 84 (86.60%) had 500-2 × 10 6 IU/mL HBV-DNA levels, and 13 (13.40%) had less 500 IU/mL HBV-DNA levels. Laboratory indicators of measurements showed the levels of white blood count, serum TBIL and PTA, and serum sodium and creatinine were also indicated.…”

Section: Statistics and Analysismentioning

confidence: 99%

Peripheral T Lymphocytes Predict the Severity and Prognosis in Patients with HBV-Related Acute-On-Chronic Liver Failure

Zhang

Wang

Sun

et al. 2020

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Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening syndrome with high mortality. Biomarkers are urgently needed to predict the prognosis of HBV-ACLF. Recent evidence suggests a key role for immune system in the pathology of HBV-ACLF. Here, we analyzed the correlation between peripheral blood T lymphocytes and the severity and prognosis in HBV-ACLF patients.Methods Sixty-six patients with HBV-ACLF received conventional medical treatments for four weeks. Twenty-three healthy subjects and 23 HBV patients were enrolled for comparison. We determined white blood cell count, lymphocytes, CD3+, CD4+ and CD8+ T cells, and CD4+CD25+ Treg cells in the blood of all subjects. Their associations with laboratory parameters before or after treatments were statistically analyzed.Results The results showed that compare normal subjects and chronic hepatitis B patients, HBV-ACLF patients had significantly increased white blood count, CD4+ T cells and decreased lymphocytes, CD3+ T cells and Treg cells. Correlation analysis showed that white blood cell, lymphocytes and peripheral T lymphocytes were correlated with PTA and MELD scores. After treatment, white blood cell, lymphocytes, and peripheral T lymphocytes were also correlated with PTA and MELD scores. Additionally, TBIL, ALT, INR, MELD and white blood cell count were potential prognostic criteria for HBV-ACLF patients. In conclusion, HBV-ACLF patients had depletion and dysfunction of immune system. Changes of peripheral T lymphocytes were closely related to the pathogenesis and prognosis of disease.Conclusions Our results may contribute to predict the severity of HBV-ACLF, and provide a prognosis response to improve the treatment of HBV-ACLF.

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“…Cirrhosis progression End-stage fibrosis, ACLF antigen, has been elevated in both animals and patients with acute liver failure. 101 Furthermore, plasma exchange in the mouse model lowered levels of CD80 and CD86, which regulates CTLA4 expression. 101 Whether CTLA4 correlates with improved adaptive immunity and survival in liver disease remains to be seen.…”

Section: Hyperinflammatory Immunosuppressionmentioning

confidence: 99%

Acute on Chronic Liver Failure and Immune Dysfunction: A Mimic of Sepsis

Hensley

Deng

2018

Semin Respir Crit Care Med

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Both the adaptive and innate arms of immunity are altered in patients with cirrhosis, which have both prognostic and clinical implications. Acute on chronic liver failure (ACLF), defined as decompensated cirrhosis with associated organ failure, carries a high risk of 28-day mortality and is marked by a significant inflammatory response. Patients with decompensated chronic liver disease display a shift from a chronic low-grade inflammatory state to one of intense inflammation, followed by the development of immunoparalysis. Considerable heterogeneity exists depending on the nature of the inciting cause and duration of ACLF. In this review, we will highlight the changes that immune cell populations in the liver undergo during decompensated liver disease, underscoring the immunological paradox between inflammation and increased susceptibility to infection that occurs during ACLF and progressive cirrhosis, as well as provide future perspectives regarding potentially useful biomarkers and possible avenues for treatment.

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Increased Expression of Cytotoxic T-Lymphocyte−Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure

Cited by 43 publications

References 47 publications

CD8+ T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction

CD8+ T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction

Peripheral T Lymphocytes Predict the Severity and Prognosis in Patients with HBV-Related Acute-On-Chronic Liver Failure

Acute on Chronic Liver Failure and Immune Dysfunction: A Mimic of Sepsis

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