Reversal of T Cell Exhaustion in Chronic HCV Infection

Abstract

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.

Ex Vivo Blockade of the PD-1 Pathway Improves Recall IFNγ Responses of HIV-Infected Persons on Antiretroviral Therapy

“…Moreover, we did not assess the effect of blocking the PD-1 pathway on recall responses of HIV-uninfected persons. Therefore, we could not exclude the possibility that targeting the PD-1 pathway could boost recall IFNγ responses of HIV-uninfected persons, particularly those with factors that are known to induce T cell exhaustion, such as viral hepatitis [ 35 ] or aging [ 27 ].…”

Assessment of neutrophil subsets and immune checkpoint inhibitor expressions on T lymphocytes in liver transplantation: A preliminary study beyond the neutrophil-lymphocyte ratio

“…Engagement of PD-1 and TIM3 pathways on T lymphocytes leads to the inhibition of the second signal of T cell activation. High and sustained expression of the co-inhibitory molecules during persistent antigen stimulation has been shown to promote immune cells exhaustion in cancer, sepsis ( Rienzo et al, 2022 ) and chronic hepatitis B and C ( Osuch et al, 2020 ; Li et al, 2022 ). Several studies described a slight increase in PD-1 and/or TIM-3 lymphocyte expressions in acute alcoholic hepatitis/cirrhosis ( Markwick et al, 2015 ; Lebossé et al, 2019 ; Riva et al, 2021 ; Fadriquela et al, 2022 ).…”

Metabolic dysfunction and cancer in HCV: Shared pathways and mutual interactions

“…Cytotoxic CD8+ T cells are the predominant cell type responsible for clearing HCV infected hepatocytes. During HCV infection, effector CD8+ T cells become progressively exhausted due to persistent antigen exposure and as a result exhibit reduced antiviral activity 131,132 . This T cell exhaustion does not resolve following DAA treatment 133 .…”