Table 1.

Costimulatory molecules involved in delayed-type hypersensitivity.

Costimulatory molecules	Implicated cells in DTH	Ligand/receptors	Ligand/receptors expression	Types of DTH	Study designs
CD28	T cells (including Tregs)	CD80, CD86	APCs	SJS/TEN; CHS; abacavir hypersensitivity	Animal study (52–55)
OX40	Tregs, conventional T cells	OX40L	APCs	CHS; DRESS/DIHS	Case control (56, 57); case series (58); animal study (59, 60)
CD40	Activated T cells, APCs	CD40L	APCs, activated T cells	CHS; sulfamethoxazole hypersensitivity; SJS/TEN; amoxicillin/amoxicillin-clavulanic acid DTH; anti-epileptic-induced hypersensitivity	Case control (61, 62); case series (63); animal study (64–66); in vitro study (67)
CD226	T cells, APCs	CD155	APCs, T cells	CHS	Animal study (68); in vitro study (69)
CD137/4-1BB	Activated T cells	CD137L/4-1BBL	CD14+CD16+ Monocyte, APCs	SJS/TEN	Case series (70)
GITR	Epidermal keratinocytes, T cells (including Tregs)	GITRL	APCs	CHS	Animal study (71)
CD94/NKG2C	NK cells, Cytotoxic T cells	HLA-E	Keratinocytes	SJS/TEN	Case control (72)

DTH, delayed-type hypersensitivity; CD28, cluster of differentiation 28; APC, antigen-presenting cell; CHS, contact hypersensitivity; SJS/TEN, Stevens-Johnson syndrome/toxic epidermal necrolysis; OX40L, OX40 ligand; DRESS/DIHS, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome; GITR(L), glucocorticoid induced TNF receptor (ligand); NK cells, natural killer cells; HLA-E HLA class I histocompatibility antigen, alpha chain E.