Role of regulatory T-cells during hepatitis C infection: From the acute phase to post-transplantation recurrence

Abstract

Hepatitis C viral infection persists and becomes chronic in a majority of affected individuals. Numerous factors have been described to explain how the virus manages to escape the host immune system. One important escape mechanism is the increase in regulatory T cells induced by the virus. In this review, we will focus on the status of regulatory T cells throughout the natural history of hepatitis C infection and after liver transplantation. The molecular mechanisms involved in increasing the number of regulatory T cells are also discussed, as are data regarding the impact of regulatory T-cells on hepatic fibrosis in the context of hepatitis C viral infection.

Dynamic balance of pro‐ and anti‐inflammatory signals controls disease and limits pathology

“…Regulatory T cells are important in controlling the balance between host damage and viral control and are induced following galectin‐9 production by KCs . Alternatively, Tregs have also been associated with inducing chronic infection and the virus itself can use this pathway to promote immune tolerance . Thorough reviews of the immune response to HCV response are available for more details …”

“…198 Alternatively, Tregs have also been associated with inducing chronic infection 199 and the virus itself can use this pathway to promote immune tolerance. 200 Thorough reviews of the immune response to HCV response are available for more details. 201,202 Much of the modeling work on HCV infection focuses on viral kinetics and uses target-cell-limited models to determine the effect that the immune response may have on controlling the virus in the presence of HIV co-infection and does not specially examine the role of pro-and anti-inflammatory cells and mediators in HCV infection.…”

Regulatory T cell therapy: An option to induce operational tolerance in liver transplantation

“…mTOR inhibitors, sirolimus or everolimus, are clearly the pivotal drugs to be used to favor the development and phenotype maintenance of Treg [39]. By contrast, corticosteroids, antimetabolite drugs such as azathioprine, and calcineurin inhibitors may impair the development or Treg [8,15,40,41]. Anti-CD25 monoclonal antibodies might be deleterious on the development of CD4+CD25+FoxP3+ cells, but no data are available.…”

“…By contrast, OT takes place only after several years [7]. OT may rely on Treg, but also probably on B cells, NK/NKT cells, myeloid-derived suppressor cells and tolerogenic dendritic cells [15][16][17][18]. OT is not a definitive status, and rejection may occur after years [3,7].…”

Lymphocyte Landscape after Chronic Hepatitis C Virus (HCV) Cure: The New Normal

“…CD4 + Tregs, defined as CD4 + CD25 + CD127 low Foxp3 + cells, are a specialized T cell population that inhibit the activation, proliferation, differentiation, and effector functions of multiple immune cell types, including T cells, B cells, NK cells, and dendritic cells [ 119 , 120 , 121 , 122 ]. Once activated, they exert their suppressive function in a non-specific manner through cell-to-cell contact inhibition and production of regulatory cytokines TGFβ, IL10, and IL35 [ 123 ]. In CHC, CD4 + Treg frequency gradually expands, resulting in reduced overall antiviral immune responses.…”