Life, activation and death of intrahepatic lymphocytes in chronic hepatitis C

Valiante, Nicholas M.; D’Andrea, Annalisa; Crotta, Stefania; Lechner, Franziska; Klenerman, Paul; Nuti, Sandra; Wack, Andreas; Abrignani, Sergio

doi:10.1034/j.1600-0528.2002.017417.x

Cited by 85 publications

(75 citation statements)

References 51 publications

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“…Moreover, these cells contained large amounts of perforin prestored in intracytoplasmic vesicles (Table II) and were able to exert HCV-specific cytotoxicity directly ex vivo without the need of additional restimulation (Table II). Importantly, T cells with down-regulated CD28 expression have also recently been demonstrated in the liver of patients with chronic hepatitis C (29). Our data suggest that they may contribute to liver injury based on their cytotoxic effector functions, but may be unable to completely eradicate the virus because proliferation ( Fig.…”

Section: Phenotypic and Functional Analysis Of Hcv-specific Cd8mentioning

confidence: 79%

Impaired Effector Function of Hepatitis C Virus-Specific CD8+ T Cells in Chronic Hepatitis C Virus Infection

Wedemeyer

Nascimbeni

et al. 2002

The Journal of Immunology

593

478

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The cellular immune response contributes to clearance of hepatitis C virus (HCV) and persists for decades after recovery from infection. The immunological basis for the inefficiency of the cellular immune response in chronically infected persons is not known. Here, we used four HLA-A2 tetramers, specific for two HCV core and two HCV NS3 epitopes, to investigate at the single-cell level effector function and phenotype of HCV-specific CD8+ T cells in 20 chronically infected and 12 long-term recovered patients. Overall, HCV-specific, tetramer+ T cells were more frequently found in PBMCs of chronically infected patients than in those of recovered patients. However, when compared with HCV-tetramer+ T cells of recovered patients, they displayed an impaired proliferative capacity. As a result of the impaired proliferative capacity, HCV-specific T cell lines derived from chronically infected patients displayed less peptide-specific cytotoxicity than those from recovered patients. In addition, proliferation and ex vivo IFN-γ production of HCV-tetramer+ cells, but not influenza-virus-specific T cells, were defective in chronically infected patients and could not be restored by in vitro stimulation with peptide and IL-2. At least three distinct phenotypes of HCV-specific CD8+ T cells were identified and associated with certain functional characteristics. In addition, impairment of proliferative, cytokine, and cytotoxic effector functions of tetramer+ T cells in viremic patients was associated with weak ex vivo HCV-specific CD4+ T cell responses. Thus, the defective functions of HCV-specific CD8+ T cells might contribute to viral persistence in chronically infected patients, and knowledge on their reversibility may facilitate the development of immunotherapeutic vaccines.

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Section: Phenotypic and Functional Analysis Of Hcv-specific Cd8mentioning

confidence: 79%

Impaired Effector Function of Hepatitis C Virus-Specific CD8+ T Cells in Chronic Hepatitis C Virus Infection

Wedemeyer

Nascimbeni

et al. 2002

The Journal of Immunology

593

478

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“…1). After infection, viral replication takes place within the liver and at this stage is influenced by host innate immune responses, including interferon alpha and intrahepatic lymphocyte populations, such as NK and NKT cells [63,64]. Viral antigen is presented within the liver and in lymphoid organs.…”

Section: Success Versus Failure Of T Cell Responses: the Potential Romentioning

confidence: 99%

Cellular immune responses against hepatitis C virus: the evidence base 2002

Ward¹,

Lauer

Isba³

et al. 2002

Clinical and Experimental Immunology

137

102

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SUMMARYHepatitis C virus (HCV) is an RNA virus which is estimated to persistently infect about 170 million people worldwide. After acute infection, there is an initial period during which long-term outcome is decided. There is strong evidence that the cellular immune responses, involving both CD4 + and CD8 + T lymphocytes, are involved at this stage and it is their effectiveness which determines outcome. What is not understood is what determines their effectiveness. The most important component of this is likely to be some aspect of epitope selection, itself dictated by host MHC. Thus, to understand host immunity to HCV, we need to have a detailed understanding of the peptides involved in T lymphocyte responses. In this review, we discuss the peptide epitopes that have been identified so far, and their potential significance. We relate this to a scheme of host defence which may be useful for understanding natural and vaccine-induced immunity.

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“…It was previously shown that T cells, NKT cells and NK cells accumulate in the liver during HCV infection [2][3][4].…”

Section: Cxcl12 Is a Highly Potent Chemoattractant For Pbl Derived Frmentioning

confidence: 99%

“…During such inflammatory processes, significant numbers of CD4 T cells, CD8 T cells, NKT cells and NK cells accumulate in the human liver relative to peripheral blood [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus

Wald¹,

et al. 2004

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Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is accompanied by inflammation and fibrosis eventually leading to cirrhosis. The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV-and HBV-associated liver inflammation and fibrosis was therefore studied. The levels and tissue localization of CXCL12 in liver and plasma of HCV and HBV patients were tested using immunohistochemistry and ELISA. The expression and function of CXCR4 on liver-infiltrating lymphocytes (LIL) were tested by FACS and transwell migration assays. We found that CXCL12 is expressed by bile duct epithelial cells in normal liver tissue. Bile duct proliferation and liver fibrosis in chronic HCV and HBV infection result in the anatomical re-distribution of CXCL12 in the liver. Moreover, CXCL12 is up-regulated in the endothelium of neo-bloodvessels formed in active inflammatory foci and is significantly elevated, compared with controls, in the plasma of patients with advanced liver fibrosis. Complementing these observations were others indicating that over 50% of LIL express CXCR4 and, in response to CXCL12, migrated and adhered to fibronectin. These observations suggest an important role for the CXCL12/CXCR4 pathway in recruitment and retention of immune cells in the liver during chronic HCV and HBV infection.

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Life, activation and death of intrahepatic lymphocytes in chronic hepatitis C

Cited by 85 publications

References 51 publications

Impaired Effector Function of Hepatitis C Virus-Specific CD8+ T Cells in Chronic Hepatitis C Virus Infection

Impaired Effector Function of Hepatitis C Virus-Specific CD8+ T Cells in Chronic Hepatitis C Virus Infection

Cellular immune responses against hepatitis C virus: the evidence base 2002

Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus

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