Towards a Systems Immunology Approach to Understanding Correlates of Protective Immunity against HCV

Shoukry, Naglaa H.

doi:10.3390/v13091871

Cited by 5 publications

(5 citation statements)

References 110 publications

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“…Given the important role of CD8+ T cells in HCV and HBV clearance, an in-depth examination of the CD8+ T cell response in both infected patients and animal models over the last decades has given more profound insights into the components of a successful CD8+ T cell effector response (reviewed [ 14 , 75 , 76 ]). Overall, studies from acutely infected patients, mostly examining peripheral blood-derived virus-specific CD8+ T cells, have shown that viral clearance is associated with the delayed emergence (4–8 weeks post-infection) of a CD8+ T cell response targeting multiple epitopes and exerting diverse effector functions, such as cytokine production and cytolytic activity [ 76 ].…”

Section: Hepatic T Cell Subsets During Acute-resolving Viral Hepatitismentioning

confidence: 99%

“…Overall, studies from acutely infected patients, mostly examining peripheral blood-derived virus-specific CD8+ T cells, have shown that viral clearance is associated with the delayed emergence (4–8 weeks post-infection) of a CD8+ T cell response targeting multiple epitopes and exerting diverse effector functions, such as cytokine production and cytolytic activity [ 76 ]. While acute clearance of HCV leads to the development of long-lasting memory CD8+ T cells, both chimpanzees and humans remain susceptible to reinfection, indicating the formation of limited protective immunity [ 14 , 75 ].…”

Section: Hepatic T Cell Subsets During Acute-resolving Viral Hepatitismentioning

confidence: 99%

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Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

2023

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T cells play an important role in the clearance of hepatotropic viruses but may also cause liver injury and contribute to disease progression in chronic hepatitis B and C virus infections which affect millions of people worldwide. The liver provides a unique microenvironment of immunological tolerance and hepatic immune regulation can modulate the functional properties of T cell subsets and influence the outcome of a virus infection. Extensive research over the last years has advanced our understanding of hepatic conventional CD4+ and CD8+ T cells and unconventional T cell subsets and their functions in the liver environment during acute and chronic viral infections. The recent development of new small animal models and technological advances should further increase our knowledge of hepatic immunological mechanisms. Here we provide an overview of the existing models to study hepatic T cells and review the current knowledge about the distinct roles of heterogeneous T cell populations during acute and chronic viral hepatitis.

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Section: Hepatic T Cell Subsets During Acute-resolving Viral Hepatitismentioning

confidence: 99%

Section: Hepatic T Cell Subsets During Acute-resolving Viral Hepatitismentioning

confidence: 99%

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

2023

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“…3 b). The central role of virus-specific CD8 + T cells in the clearance of acute viral infection and virus-associated liver injury is now well established [ 119 , 120 ]. For example, CD8 + T cells and NK cells clear infected cells by secreting antiviral cytokines (e.g., IFN-γ) and with perforin-dependent cytotoxic effects, but this leads to indiscriminate liver injury [ 121 , 122 ].…”

Section: Imbalance Of Liver Immune Microenvironment and Liver Diseasesmentioning

confidence: 99%

Mesenchymal stem cells-based therapy in liver diseases

Han

Jin

2022

Mol Biomed

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Multiple immune cells and their products in the liver together form a complex and unique immune microenvironment, and preclinical models have demonstrated the importance of imbalances in the hepatic immune microenvironment in liver inflammatory diseases and immunocompromised liver diseases. Various immunotherapies have been attempted to modulate the hepatic immune microenvironment for the purpose of treating liver diseases. Mesenchymal stem cells (MSCs) have a comprehensive and plastic immunomodulatory capacity. On the one hand, they have been tried for the treatment of inflammatory liver diseases because of their excellent immunosuppressive capacity; On the other hand, MSCs have immune-enhancing properties in immunocompromised settings and can be modified into cellular carriers for targeted transport of immune enhancers by genetic modification, physical and chemical loading, and thus they are also used in the treatment of immunocompromised liver diseases such as chronic viral infections and hepatocellular carcinoma. In this review, we discuss the immunological basis and recent strategies of MSCs for the treatment of the aforementioned liver diseases. Specifically, we update the immune microenvironment of the liver and summarize the distinct mechanisms of immune microenvironment imbalance in inflammatory diseases and immunocompromised liver diseases, and how MSCs can fully exploit their immunotherapeutic role in liver diseases with both immune imbalance patterns.

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“…The hepatic immune system is thought to play both, protective and detrimental roles in inflammatory liver diseases (6,7). While hepatic immune responses are essential for the clearance of HCV infection, they also contribute to liver injury and to the progression of liver disease in viral hepatitis (8,9). A better understanding of the mechanisms that regulate the development of an effective antiviral immune response and the balance between tissue damage and protection during inflammation is a prerequisite for the development of HCV vaccination strategies and therapeutic options for the treatment of advanced liver disease.…”

Section: Introductionmentioning

confidence: 99%

Hepatic iNKT cells produce type 2 cytokines and restrain antiviral T cells during acute hepacivirus infection

et al. 2022

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Chronic hepatitis C virus (HCV) infection is a curable disease, but the absence of a vaccine remains a major problem in infection prevention. The lack of small animal models and limited access to human liver tissue impede the study of hepatic antiviral immunity and the development of new vaccine strategies. We recently developed an immune-competent mouse model using an HCV-related rodent hepacivirus which shares immunological features with human viral hepatitis. In this study, we used this new model to investigate the role of invariant natural killer T (iNKT) cells during hepacivirus infection in vivo. These cells are enriched in the liver, however their role in viral hepatitis is not well defined. Using high-dimensional flow cytometry and NKT cell deficient mice we analyzed a potential role of iNKT cells in mediating viral clearance, liver pathology or immune-regulation during hepacivirus infection. In addition, we identified new immune-dominant MHC class I restricted viral epitopes and analyzed the impact of iNKT cells on virus-specific CD8+ T cells. We found that rodent hepacivirus infection induced the activation of iNKT cell subsets with a mixed NKT1/NKT2 signature and significant production of type 2 cytokines (IL-4 and IL-13) during acute infection. While iNKT cells were dispensable for viral clearance, the lack of these cells caused higher levels of liver injury during infection. In addition, the absence of iNKT cells resulted in increased effector functions of hepatic antiviral T cells. In conclusion, our study reports a regulatory role of hepatic iNKT cells during hepacivirus infection in vivo. Specifically, our data suggest that iNKT cells skewed towards type 2 immunity limit liver injury during acute infection by mechanisms that include the regulation of effector functions of virus-specific T cells.

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Towards a Systems Immunology Approach to Understanding Correlates of Protective Immunity against HCV

Cited by 5 publications

References 110 publications

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

Mesenchymal stem cells-based therapy in liver diseases

Hepatic iNKT cells produce type 2 cytokines and restrain antiviral T cells during acute hepacivirus infection

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