Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus

By F. Lechner, David K. Wong, P. Dunbar, R. Chapman, Raymond T. Chung, P. Dohrenwend, G. Robbins, R. Phillips, P. Klenerman, Bruce D. Walker. Journal of Experimental Medicine, 2000

1,377 citations recorded by the source corpus.

Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-γ, a “stunned” phenotype, from which they recovered as viremia declined. In long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection.

Subfields: Hepatology, Immunology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/44a901e294fa4b49e95eba2b95c0398737c6a4cd

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Citations in the corpus

Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever (2003, neutral): “A similar pattern is seen in hepatitis C virus infection: antigen-specific T cells, although relatively prevalent, do not produce IFN-γ during an acute infection and the response returns 10 weeks later, after viral clearanc”
Mechanism of action of interferon and ribavirin in treatment of hepatitis C (2005, background): “In addition to direct immune stimulation, by decreasing HCV RNA replication, IFN might prevent immune exhaustion and enhance the adaptive HCV-specific immune respons”
Memory CD8 T-Cell Differentiation during Viral Infection (2004, background): “Cells in this state are incapable of ex vivo cytotoxicity and IL-2 and TNF- production and have now also completely lost the ability to synthesize IFN- in response to peptide stimulation (37, 70, 71, 129, 138).”
Genetic diversity and evolution of hepatitis C virus--15 years on. (2004, background): “Indeed, recovery from infection is associated with strong and sustained CTL responses around the time of primary infection (Cooper et al., 1999; Lechner et al., 2000; Thimme et al., 2001), a time where there is evidence for specific changes in CTL epitopes and accelerated sequence change in the codi”
The Natural History of Hepatitis C Virus (HCV) Infection (2006, background): “Evidence for this comes mostly from retrospective analyses of two large outbreaks of hepatitis C that occurred among pregnant women who received Rh immune globulin that had been contaminated with HCV.”
T cell exhaustion (2011, background): “In contrast, during chronic HCV infection, CD8 + T cells that cannot make IFN-γ have been reporte”
CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer. (2019, background): “Altered memory homeostasis is also likely a feature of Tex cells in humans because in HIV and HCV infection many Tex cells are lost following antiviral therapy or viral escape, suggesting an antigen-dependent lifestyle, though a small subset of these cells may persist after viral cure or escape (86–”
Memory CD8+ T Cells Are Required for Protection from Persistent Hepatitis C Virus Infection (2003, background): “HCV-specific CD4 T cells are absent or transiently present in the blood (2, 4, 5, 7, 8), do not accumulate in substantial numbers in the liver (2), and may be skewed toward production of regulatory rather than antiviral cytokines (9).”
Immunology of hepatitis B virus and hepatitis C virus infection (2005, background): “By contrast, patients with chronic hepatitis B or hepatitis C tend to have late, transient or narrowly focused T-cell response”