Table II.

Immunological characteristics and clinical manifestations following upregulation of CTLA-4.

Status	Immunological characteristics			Compared with healthy controls	Clinical manifestations	(Refs.)
	Cells	Cytokines	Molecules
Immune clearance	CD8+T, Th1 CD8+ CTL, TFH	IL-2, IFN-γ, TNF-α, GM-CS, IL-1β, IL-21, perforin, granzyme, CCL3	CD28, CD80/CD86 Lck, TCR, PCKθ	Decreased	Mild liver damage, but poor response to HBV proteins	(6,22,25,27,28,39,43, 48,55,81,83,84)
Immune tolerance	Treg, Th2	IL-10, TGF-β	PD-1, CTLA-4, Bim	Increased	Low-grade inflammation, but led to T cell exhaustion and apoptosis	(29,32,62,63, 64,66,70)

CTLA-4, cytotoxic T lymphocyte-associated antigen-4; Th, T helper cells; CTL, cytotoxic T cell; TFH, follicular helper T cells; Treg, regulatory T cell; IL, interleukin; IFN, interferon; TNF, tumor necrosis factor; GM-CSF, granulocyte-macrophage colony stimulating factor; CCL3, C-C motif chemokine ligand 3; TGF, transforming growth factor; Lck, transforming growth factor; TCR, T cell receptor; PCKθ, protein kinase Cθ; PD-1, programmed cell death-1; HBV, hepatitis B virus.