TIM-3 as a marker of exhaustion in CD8+ T cells of active chronic hepatitis B patients

2019 ◽  
Vol 128 ◽  
pp. 323-328 ◽  
Author(s):  
Hiva Mohammadizad ◽  
Mehdi Shahbazi ◽  
Mohammad Reza Hasanjani Roushan ◽  
Mehdi Soltanzadeh-Yamchi ◽  
Mousa Mohammadnia-Afrouzi
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Cd8 T Cells ◽  
Active Chronic Hepatitis

scholarly journals In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2273
Author(s):  
Katrin Manske ◽  
Annika Schneider ◽  
Chunkyu Ko ◽  
Percy A. Knolle ◽  
Katja Steiger ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Cd8 T Cells ◽  
Recombinant Adenovirus ◽  
Hbv Infection ◽  
High Dose ◽  
Viral Immunity

Immunity against hepatitis B virus (HBV) infection is complex and not entirely understood so far, including the decisive factors leading to the development of chronic hepatitis B. This lack of a mechanistic understanding of HBV-specific immunity is also caused by a limited number of suitable animal models. Here, we describe the generation of a recombinant adenovirus expressing an HBV 1.3-overlength genome linked to luciferase (Ad-HBV-Luc) allowing for precise analysis of the quantity of infected hepatocytes. This enables sensitive and close-meshed monitoring of HBV-specific CD8 T cells and the onset of anti-viral immunity in mice. A high dose of Ad-HBV-Luc developed into chronic hepatitis B accompanied by dysfunctional CD8 T cells characterized by high expression of PD1 and TOX and low expression of KLRG1 and GzmB. In contrast, a low dose of Ad-HBV-Luc infection resulted in acute hepatitis with CD8 T cell-mediated elimination of HBV-replicating hepatocytes associated with elevated sALT levels and increased numbers of cytotoxic HBV-specific CD8 T cells. Thus, the infectious dose was a critical factor to induce either acute self-limited or chronic HBV infection in mice. Taken together, the new Ad-HBV-Luc vector will allow for highly sensitive and time-resolved analysis of HBV-specific immune responses during acute and chronic infection.

scholarly journals Unraveling the Multifaceted Nature of CD8 T Cell Exhaustion Provides the Molecular Basis for Therapeutic T Cell Reconstitution in Chronic Hepatitis B and C

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2563
Author(s):  
Valeria Barili ◽  
Andrea Vecchi ◽  
Marzia Rossi ◽  
Ilaria Montali ◽  
Camilla Tiezzi ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
T Cell ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Cd8 T Cells ◽  
Stress Responses ◽  
T Cell Exhaustion ◽  
Virus Infections ◽  
Cell Exhaustion

In chronic hepatitis B and C virus infections persistently elevated antigen levels drive CD8+ T cells toward a peculiar differentiation state known as T cell exhaustion, which poses crucial constraints to antiviral immunity. Available evidence indicates that T cell exhaustion is associated with a series of metabolic and signaling deregulations and with a very peculiar epigenetic status which all together lead to reduced effector functions. A clear mechanistic network explaining how intracellular metabolic derangements, transcriptional and signaling alterations so far described are interconnected in a comprehensive and unified view of the T cell exhaustion differentiation profile is still lacking. Addressing this issue is of key importance for the development of innovative strategies to boost host immunity in order to achieve viral clearance. This review will discuss the current knowledge in HBV and HCV infections, addressing how innate immunity, metabolic derangements, extensive stress responses and altered epigenetic programs may be targeted to restore functionality and responsiveness of virus-specific CD8 T cells in the context of chronic virus infections.

Upregulation of CXCR3 expression on CD8+ T cells due to the pervasive influence of chronic hepatitis B and C virus infection

2013 ◽  
Vol 74 (8) ◽  
pp. 899-906 ◽  
Author(s):  
A. de Niet ◽  
J. de Bruijne ◽  
M.J. Tempelmans Plat-Sinnige ◽  
R.B. Takkenberg ◽  
R.A.W. van Lier ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Virus Infection ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Cd8 T Cells ◽  
Cxcr3 Expression

scholarly journals The Reduction in CD8+PD-1+ T Cells in Liver Histological Tissue is Related to Pegylated IFN-α Therapy Outcomes in Chronic Hepatitis B Patients

2020 ◽  
Author(s):  
Ruyu Liu ◽  
Yanhui Chen ◽  
Jiang Guo ◽  
Minghui Li ◽  
Yao Lu ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Mononuclear Cells ◽  
Hbeag Seroconversion ◽  
Active Chronic Hepatitis ◽  
Median Frequency ◽  
Inflammation Response ◽  
Significant Difference

Abstract Background and Aim: Antiviral therapy is recommended for patients with immune-active chronic hepatitis B (CHB) to decrease the risk of liver-related complications. However, the outcomes of the pegylated IFN-α (PEG-IFN-α) therapy vary among CHB patients. We aimed to identify factors that can influence the outcomes in CHB patients who received antiviral PEG-IFN-α monotherapy. Methods: Thirty-two CHB patients who received PEG-IFN-α monotherapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months after the initiation of the therapy. CD8+ T cells, CD4+ T cells, CD68+ mononuclear cells, and PD-1 levels in the 64 liver biopsy specimens were examined via immunofluorescence. Results: The overall median frequency of CD8+ T cells in the liver tissues of 32 CHB patients significantly decreased at 6 months after the therapy initiation (p < 0.01). In the FIER (fibrosis and inflammation response with HBeAg seroconversion) group, CD8+PD-1+ T cells significantly decreased at 6 months (p < 0.05), while CD8+PD-1- T cells had no significant difference. On the contrary, in the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group, CD8+PD-1- T cells significantly decreased after 6 months of PEG-IFN-α treatment (p < 0.05), while CD8+PD-1+ T cells had no significant difference. In addition, the levels of CD68+ mononuclear cells in the FIER group showed an overall increasing trend after treatment (p < 0.05). Conclusions: The changes in the levels of CD8+PD-1+ T cells and CD68+ mononuclear cells may be related to the response to PEG-IFN-α therapy.

The impact of HBV-DNA fluctuations on virus-specific CD8+ T cells in HBeAg+ chronic hepatitis B patients treated with a steroid and lamivudine

2006 ◽  
Vol 13 (6) ◽  
pp. 415-425 ◽  
Author(s):  
J. Gotto ◽  
G. J. M. Webster ◽  
D. Brown ◽  
J. Jenkins ◽  
G. M. Dusheiko ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Cd8 T Cells ◽  
Hbv Dna ◽  
The Impact
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