Tolerogenic Dendritic Cells on Transplantation: Immunotherapy Based on Second Signal Blockage

Table 1

Immunotherapy based on the second signal blockage.

Molecule	Commercial name/clone	Target molecule	Mechanism of action	References
CTLA4-Ig	Abatacept/Belatacept	CD80/CD86	Competition for binding to B7 molecules on DC; Upregulation of IDO enzyme expression; High plasma levels of sHLA-G; High secretion of immunomodulatory cytokines; Inhibition of CD8^+ T cells and NK cells; Generation of Treg cells; Inhibition of proliferation related to p27kip1 expression	[88, 107–123]
CTLA4-KDEL	—	CD80/CD86	Retention of costimulatory molecules within the ER; T cell anergy by an IDO-independent way	[72, 115]
Anti-CD40L (CD154)/anti-CD40	3A8, 4D11, ASKP1240, 7E1	CD40/CD40L	Inhibition of antibody secretion; Downregulation of T cell proliferation; Inhibition of cytokine secretion and costimulatory molecule synthesis; Upregulation of spleen IL-10^+CD4^+; T cells and downregulation of IFN-γ^+CD4^+ T cells	[117, 123–135]
PD-L1.Ig	—	PD-1/PD-1L	Suppression of T cell activation	[136–138]
Anti-TIM-1	RMT1-10	TIM-1	Blockage of TIM-1 ligation	[139–141]
Anti-OX40-L	—	OX40-OX40L interaction	Inhibition of OX40-OX40L signaling; Prevention of T memory cells; Reduction of effector T cells	[128, 129, 142, 143]
LFA3-Ig	Alefacept	LFA3 (CD58)	Depletion of CD8^+ effector memory T cells; Reduction of T cell activation	[113, 116, 144–146]