Restoring homeostasis of CD4+ T cells in hepatitis-B-virus-related liver fibrosis

Table 2 Role of surface molecules in chronic hepatitis

Surface molecules	Expression on T cells and CD4+ T cell subsets	General effects	Role in liver inflammation and fibrosis	CD4+ T cell response to blocking	Ref.
PD-1	CD8+ T cells	Inhibits T cell activation;	Causes exhaustion of HBV-specific CD8+ and CD4+ T cells	Partially-revived proliferation and function	[96-98,104]
	CD4+ T cells	Maintains tolerance
TIM-3	CD8+ T cells	Inhibits T cell activation; Maintains tolerance	Promotes progression of HBV infection	Revived more (blocked with PD-1)	[99,100,102-104]
	CD4+ T cells
	Treg cells
CTLA-4	Activated CD4+ T cells	Inhibits CD4+ T cell over-activation;	Promotes persistence of HBV and progression of HBV infection	Unknown	[105,107,109,110]
	Treg cells	Maintains tolerance
CB2	CD4+ T cells	Immunoregulatory: pro-inflammatory or anti-inflammatory; Anti-fibrotic	Anti-inflammatory;Anti-fibrotic;Hepatoprotective?	Decreased frequency and function of Th17 cells	[112-114]
	CD8+ T cells
	Th17 cells

PD-1: Programmed cell-death protein 1; CTLA-4: Cytotoxic T lymphocyte-associated antigen 4; TIM-3: T-cell immunoglobulin domain and mucin domain-containing molecule 3; CB2: Cannabinoid receptor 2; HBV: Hepatitis B virus.