Journal Article

Reversal of T Cell Exhaustion in Chronic HCV Infection

Caraballo Cortés, Kamila, Osuch, Sylwia, Metzner, Karin J.

2020

Overview

The long-term consequences of T cell responses’ impairment in chronic HCV infection are not entirely characterized, although they may be essential in the context of the clinical course of infection, re-infection, treatment-mediated viral clearance and vaccine design. Furthermore, it is unclear whether a complete reinvigoration of HCV-specific T cell response may be feasible. In most studies, attempting to reverse the effects of compromised immune response quality by specific blockades of negative immune regulators, a restoration of functional competence of HCV-specific T cells was shown. This implies that HCV-induced immune dysfunction may be reversible. The advent of highly successful, direct-acting antiviral treatment (DAA) for chronic HCV infection instigated investigation whether the treatment-driven elimination of viral antigens restores T cell function. Most of studies demonstrated that DAA treatment may result in at least partial restoration of T cell immune function. They also suggest that a complete restoration comparable to that seen after spontaneous viral clearance may not be attained, pointing out that long-term antigenic stimulation imprints an irreversible change on the T cell compartment. Understanding the mechanisms of HCV-induced immune dysfunction and barriers to immune restoration following viral clearance is of utmost importance to diminish the possible long-term consequences of chronic HCV infection.

• Publisher: MDPI AG,MDPI
• Subject: Antigens / Antiviral Agents - therapeutic use / Antiviral drugs / CD8-Positive T-Lymphocytes - drug effects / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - pathology / chronic HCV infection / chronic hepatitis C / Chronic infection / Cytotoxicity / direct acting antivirals / disease course / Epigenetics / Hepacivirus - drug effects / Hepatitis C / Hepatitis C, Chronic - drug therapy / Hepatitis C, Chronic - immunology / HIV / Human immunodeficiency virus / Humans / Immune Checkpoint Inhibitors - therapeutic use / Immune clearance / immune response / Immunity - drug effects / Infections / inhibitory receptors / Lymphocytes / Lymphocytes T / Pathogenesis / Proteins / Review / RNA polymerase / T cell exhaustion / T-lymphocytes / Transcription factors / Tumor necrosis factor-TNF / vaccine development / viral antigens / Viral infections