Different aspects of CD4 T cells that lead to viral clearance or persistence of HCV infection

Abstract

More than 170 million people worldwide are infected with hepatitis C virus (HCV). A characteristic of this virus is a high tendency toward chronic infection. Several factors affect the viral outcome after infection. Among them, HCV-specific CD4 T cells are thought to play a crucial role in controlling viremia. Cumulative data showed that spontaneously resolved individuals have vigorous CD4 T-cell responses to a broad spectrum of HCV antigens and maintain these responses over a long period of time, whereas chronically infected patients lose their CD4 T-cell responses in the acute phase of infection. Although several possibilities of why CD4 T cells lose their function have been proposed, the mechanisms are not completely understood. Moreover, there is another subset of CD4 T cells called regulatory T cells (Tregs). These cells suppress immune reaction of T cells, B cells, and antigen-presenting cells, and are thought to protect organs from immune overreaction and autoimmunity. An increasing amount of data supports the possibility that Tregs participate in the mechanism of HCV persistence. It is obvious that CD4 T cells are the main effectors controlling HCV outcome. To achieve a better prognosis, we need to understand the mechanism of how HCV earns its chronicity by escaping from host cellular immune attacks. In this review, we will focus on the role of HCV-specific T cells in controlling viremia, particularly the aspects of these cells being either inhibitors or propellers of chronic infection.

A prospective study on Foxp3+CD25highCD4+ regulatory T cells in chronic hepatitis C infected patients undergoing direct-acting antiviral combination therapy

“…Several mechanisms of CD4+ T cell failure have been proposed and the contribution of Treg cells was established. 3 Treg cells thus limit the extent of immune-mediated liver damage associated with an excessive inflammatory process supposed to be maintained by persistent HCV infection and they have long been thought to limit hepatic fibrosis and subsequent cirrhosis resulting from such injury 25 . Nevertheless, the majority of chronic HCV carriers still possess the tendency to develop liver fibrosis and cirrhosis and ultimately hepatocellular carcinoma 26 .…”

“…This is due to their pronounced ability to suppress many cell types; effector T cells, B cells, natural killer and dendritic cells. 3 Forkhead box P3 (FoxP3) + Treg cells is the major subset of CD4+ Treg family that constitutively express the interleukin-2 (IL-2) receptor α chain (CD25), the transcription factor Foxp3 and the inhibitory receptor cytotoxic T Lymphocyte Antigen 4 (CTLA4). They also express low levels of the IL-7 receptor (CD127) 4 .…”