Historical evolution, overview, and therapeutic manipulation of co-stimulatory molecules

Table 1 Immunoglobulin super family co-stimulatory molecules

IgSF co-stimulatory molecules	Function	Cells expressing the receptor	Ligand	Cells expressing the ligand
CD28	Activation	Constitutive in T cells	CD80, CD86	CD80: Inducible in dendritic cells, monocytes, B and T cells. CD86: Constitutive in dendritic cells, monocytes, B and T cells
ICOS (CD278)	Activation	Inducible in T, B, and NK cells	ICOSL	Constitutive in macrophages, dendritic cells, B and T cells
CTLA-4 (CD152)	Inhibition	Inducible in T cells	CD80, CD86	CD80: Inducible in dendritic cells, monocytes, B and T cells. CD86: Constitutive in dendritic cells, monocytes, B and T cells
PD-1 (CD279)	Inhibition	Inducible in T, and B cells, macrophages	PD-L1, PD-L2	PD-L1: Constitutive in dendritic cells, B and T cells. PD-L2: Inducible in dendritic cells and monocytes
PD-1H (VISTA)	Inhibition	Monocytes, neutrophils, T cells	Unknown	Unknown
BTLA (CD272)	Inhibition	B and T cells	HVEM, UL144	Monocytes, B and T cells
B71 (CD80), B72 (CD86)	Activation/Inhibition	CD80: Inducible in dendritic cells, monocytes, B and T cells. CD86: Constitutive in dendritic cells, monocytes, B and T cells	CD28, CTLA-4	CD28: Constitutive in T cells. CTLA-4: Inducible in T cells
B7H1 (CD274, PDL1)	Inhibition	Constitutive in dendritic cells, monocytes, B and T cells	PD-1, B71	PD-1: Inducible in macrophages, B and T cells. CD80: Inducible in dendritic cells, monocytes, B and T cells

BTLA: B- and T lymphocyte attenuator; CTLA: Cytotoxic T lymphocyte antigen; HVEM: Herpes virus entry mediator; ICOS: Inducible T cell co-stimulator; ICOSL: Inducible T cell co-stimulator ligand; PD-1: Programmed death-1; PD-L: Programmed death ligand; PD-1H: Programmed death-1 homolog; VISTA: V domain Ig suppressor of T cell activation.