scholarly journals Gamma-Chain Receptor Cytokines & PD-1 Manipulation to Restore HCV-Specific CD8+ T Cell Response during Chronic Hepatitis C

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 538
Author(s):  
Julia Peña-Asensio ◽  
Henar Calvo ◽  
Miguel Torralba ◽  
Joaquín Miquel ◽  
Eduardo Sanz-de-Villalobos ◽  
...  
Keyword(s):  
Hepatitis C ◽  
T Cell ◽  
Cell Response ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
T Cell Response ◽  
Hcv Infection ◽  
Metabolic Reprogramming ◽  
Gamma Chain ◽  
Tcr Signalling

Hepatitis C virus (HCV)-specific CD8+ T cell response is essential in natural HCV infection control, but it becomes exhausted during persistent infection. Nowadays, chronic HCV infection can be resolved by direct acting anti-viral treatment, but there are still some non-responders that could benefit from CD8+ T cell response restoration. To become fully reactive, T cell needs the complete release of T cell receptor (TCR) signalling but, during exhaustion this is blocked by the PD-1 effect on CD28 triggering. The T cell pool sensitive to PD-1 modulation is the progenitor subset but not the terminally differentiated effector population. Nevertheless, the blockade of PD-1/PD-L1 checkpoint cannot be always enough to restore this pool. This is due to the HCV ability to impair other co-stimulatory mechanisms and metabolic pathways and to induce a pro-apoptotic state besides the TCR signalling impairment. In this sense, gamma-chain receptor cytokines involved in memory generation and maintenance, such as low-level IL-2, IL-7, IL-15, and IL-21, might carry out a positive effect on metabolic reprogramming, apoptosis blockade and restoration of co-stimulatory signalling. This review sheds light on the role of combinatory immunotherapeutic strategies to restore a reactive anti-HCV T cell response based on the mixture of PD-1 blocking plus IL-2/IL-7/IL-15/IL-21 treatment.

scholarly journals Heterologous T cell immunity in severe hepatitis C virus infection

2005 ◽  
Vol 201 (5) ◽  
pp. 675-680 ◽  
Author(s):  
Simona Urbani ◽  
Barbara Amadei ◽  
Paola Fisicaro ◽  
Massimo Pilli ◽  
Gabriele Missale ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Virus Infection ◽  
Cell Response ◽  
Cd8 T Cell ◽  
Cross Reactivity ◽  
T Cell Response ◽  
Hcv Infection ◽  
Severe Hepatitis

Hepatitis C virus (HCV) can cause liver disease of variable severity. Expansion of preexisting memory CD8 T cells by cross-reactivity with a new heterologous virus infection has been shown in mice to shape the repertoire of the primary response and to influence virus-related immunopathology (Selin, L.K. 2004. Immunity. 20:5–16). To determine whether this mechanism can influence the course of HCV infection, we analyzed the features of the HCV-specific CD8 T cell response in eight patients with acute HCV infection, two of whom had a particularly severe illness. Patients with severe hepatitis, but not those with mild disease, showed an extremely vigorous CD8 T cell response narrowly focused on a single epitope (NS3 1073–1081), which cross-reacted with an influenza neuraminidase sequence. Our results suggest that CD8 T cell cross-reactivity influences the severity of the HCV-associated liver pathology and depicts a model of disease induction that may apply to different viral infections.

Discordant Role of CD4 T-Cell Response Relative to Neutralizing Antibody and CD8 T-Cell Responses in Acute Hepatitis C

2007 ◽  
Vol 132 (2) ◽  
pp. 654-666 ◽  
Author(s):  
David E. Kaplan ◽  
Kazushi Sugimoto ◽  
Kimberly Newton ◽  
Mary E. Valiga ◽  
Fusao Ikeda ◽  
...  
Keyword(s):  
Hepatitis C ◽  
T Cell ◽  
Cell Response ◽  
Neutralizing Antibody ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Acute Hepatitis C ◽  
Cell Responses

CD8+ T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C

2016 ◽  
Vol 34 (4) ◽  
pp. 396-409 ◽  
Author(s):  
Katja Nitschke ◽  
Hendrik Luxenburger ◽  
Muthamia M. Kiraithe ◽  
Robert Thimme ◽  
Christoph Neumann-Haefelin
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hepatitis B ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Acute Infection ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Hcv Infection ◽  
T Cell Epitopes

Approximately 500 million people are chronically infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV) worldwide and are thus at high risk of progressive liver disease, leading to liver fibrosis, cirrhosis and ultimately hepatocellular cancer. Virus-specific CD8+ T-cells play a major role in viral clearance in >90% of adult patients who clear HBV and in approximately 30% of patients who clear HCV in acute infection. However, several mechanisms contribute to the failure of the adaptive CD8+ T-cell response in those patients who progress to chronic infection. These include viral mutations leading to escape from the CD8+ T-cell response as well as exhaustion and dysfunction of virus-specific CD8+ T-cells. Antiviral efficacy of the virus-specific CD8+ T-cell response also strongly depends on its restriction by specific human leukocyte antigens (HLA) class I alleles. Our review will summarize the role of HLA-A, B and C-restricted CD8+ T-cells in HBV and HCV infection. Due to the current lack of a comprehensive database of HBV- and HCV-specific CD8+ T-cell epitopes, we also provide a summary of the repertoire of currently well-described HBV- and HCV-specific CD8+ T-cell epitopes. A better understanding of the factors that contribute to the success or failure of virus-specific CD8+ T-cells may help to develop new therapeutic options for HBV eradication in patients with chronic HBV infection (therapeutic vaccination and/or immunomodulation) as well as a prophylactic vaccine against HCV infection.

scholarly journals Escape from a Dominant HLA-B*15-Restricted CD8+ T Cell Response against Hepatitis C Virus Requires Compensatory Mutations outside the Epitope

2011 ◽  
Vol 86 (2) ◽  
pp. 991-1000 ◽  
Author(s):  
M. Ruhl ◽  
P. Chhatwal ◽  
H. Strathmann ◽  
T. Kuntzen ◽  
D. Bankwitz ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Compensatory Mutations

CD8+ T-Cell Response Promotes Evolution of Hepatitis C Virus Nonstructural Proteins

2011 ◽  
Vol 140 (7) ◽  
pp. 2064-2073 ◽  
Author(s):  
Marianne Ruhl ◽  
Torben Knuschke ◽  
Kevin Schewior ◽  
Lejla Glavinic ◽  
Christoph Neumann-Haefelin ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Nonstructural Proteins

CD8+T-Cell Response Against Hepatitis C Virus

2002 ◽  
Vol 15 (1) ◽  
pp. 121-131 ◽  
Author(s):  
Xiao-Song He ◽  
Harry B. Greenberg
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response

scholarly journals Analysis of a successful HCV-specific CD8+ T cell response in patients with recurrent HCV-infection after orthotopic liver transplantation

2004 ◽  
Vol 10 (12) ◽  
pp. 1487-1496 ◽  
Author(s):  
Norbert Hubert Gruener ◽  
Maria-Christina Jung ◽  
Axel Ulsenheimer ◽  
Joern Tilman Gerlach ◽  
Reinhart Zachoval ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
T Cell ◽  
Orthotopic Liver Transplantation ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Hcv Infection

scholarly journals Human fetuses are able to mount an adultlike CD8 T-cell response

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2153-2158 ◽  
Author(s):  
Emmanuel Hermann ◽  
Carine Truyens ◽  
Cristina Alonso-Vega ◽  
Jos Even ◽  
Patricia Rodriguez ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Interferon Γ ◽  
T Cell Response ◽  
Activation Markers ◽  
T Cell Receptor Beta

Abstract Fetal/neonatal immune responses generally are considered to be immature and weaker than that of adults. We have studied the cord-blood T cells of newborns congenitally infected with Trypanosoma cruzi, the protozoan agent of Chagas disease. Our data demonstrate a predominant activation of CD8 T cells expressing activation markers and armed to mediate effector functions. The analysis of the T-cell receptor beta chain variable repertoire shows the oligoclonal expansion of these T lymphocytes, indicating that activation was driven by parasite antigens. Indeed, we have detected parasite-specific CD8 T cells secreting interferon-γ after coincubation with live T cruzi. This response is enhanced in the presence of recombinant interleukin-15, which limits the T-cell spontaneous apoptosis. These findings point out that the fetal immune system is more competent than previously appreciated, since fetuses exposed to live pathogens are able to develop an adultlike immune CD8 T-cell response.

scholarly journals Determinants of Viral Clearance and Persistence during Acute Hepatitis C Virus Infection

2001 ◽  
Vol 194 (10) ◽  
pp. 1395-1406 ◽  
Author(s):  
Robert Thimme ◽  
David Oldach ◽  
Kyong-Mi Chang ◽  
Carola Steiger ◽  
Stuart C. Ray ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Hepatitis ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Hcv Infection ◽  
Cd4 T Cell ◽  
Acute Hcv ◽  
Ifn Γ ◽  
Acute Hcv Infection

The virological and immunological features of hepatitis C virus (HCV) infection were studied weekly for 6 months after accidental needlestick exposure in five health care workers, four of whom developed acute hepatitis that progressed to chronicity while one subject cleared the virus. In all subjects, viremia was first detectable within 1–2 weeks of inoculation, 1 month or more before the appearance of virus-specific T cells. The subject who cleared the virus experienced a prolonged episode of acute hepatitis that coincided with a CD38+ IFN-γ− CD8+ T cell response to HCV and a small reduction in viremia. Subsequently, a strong CD4+ T cell response emerged and the CD8+ T cells became CD38− and started producing IFN-γ in response to HCV, coinciding with a rapid 100,000-fold decrease in viremia that occurred without a corresponding surge of disease activity. Chronic infection developed in two subjects who failed to produce a significant T cell response and in two other subjects who initially mounted strong CD4+ T cell responses that ultimately waned. In all subjects, viremia was higher at the peak of acute hepatitis than it was when the disease began, and the disease improved during the viremia. These results provide the first insight into the host–virus relationship in humans during the incubation phase of acute HCV infection, and they provide the only insight to date into the virological and immunological characteristics of clinically asymptomatic acute HCV infection, the commonest manifestation of this disease. In addition, the results suggest that the vigor and quality of the antiviral T cell response determines the outcome of acute HCV infection, that the ability of HCV to outpace the T cell response may contribute to its tendency to persist; that the onset of hepatitis coincides with the onset of the CD8+T cell response, that disease pathogenesis and viral clearance are mediated by different CD8+ T cell populations that control HCV by both cytolytic and noncytolytic mechanisms, and that there are different pathways to viral persistence in asymptomatic and symptomatic acute HCV infection.

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