Table 2.

Coinhibitory molecules involved in delayed-type hypersensitivity.

Coinhibitory molecule	Implicated cells in DTH	Ligand/receptor	Ligand/receptor expression	Type of DTH	Study designs
CTLA-4	Tregs, activated T cells	CD80, CD86	APCs	CHS; irAE; efavirenz and NSAID hypersensitivity; SMX-NO-induced hypersensitivity; delayed type liver injury to isoniazid, nevirapine, and amodiaquine	retrospective cohort study (209); case control (210, 211); case series (119, 212); case report (213); animal study (214–217); in vitro study (124)
PD-1	Tregs, activated T cells, CD8+ Trm cells	PD-L1	Tregs, conventional T cells, APCs	CHS; irAE; SMX-NO-induced hypersensitivity; delayed type liver injury to isoniazid, nevirapine, and amodiaquine	Retrospective cohort (209) study; case series (119); case report (123, 213, 218); animal study (215–217, 219); in vitro study (114, 124)
TIM-3	Tregs, activated T cells, CD8+ Trm cells	Galectin 9	APCs	SMX-NO-induced hypersensitivity; MPE; CHS	Case control (141); animal study (219); in vitro study (124)
LAG-3	Activated T cells, Tregs	MHC II	APCs	Tuberculin-induced DTH	Animal study (162)
TIGIT	T cells (including Tregs), NK cells	CD155	APCs, T cells	Keyhole limpet hemocyanin-induced DTH	Animal study (166)
BTLA	T cells	HVEM	APCs, T cells, NK cells	CHS	Animal study (220)

DTH, delayed type hypersensitivity; CTLA-4, cytotoxic T lymphocyte-associated antigen-4; Treg, regulatory T cells; APC, antigen-presenting cell; CHS, contact hypersensitivity; irAE, immune-related adverse events; NSAID, non-steroid anti-inflammatory drugs; SMX-NO, nitroso sulfamethoxazole; PD-1, programmed cell death 1; Trm cells, tissue-resident memory T cells; TIM-3, T-cell immunoglobulin mucin-3; MPE, maculopapular exanthema; LAG-3, lymphocyte activation gene-3; MHC, major histocompatibility complex; TIGIT, T cell immunoglobulin and ITIM domain; BTLA, B and T lymphocyte attenuator; HVEM, herpesvirus-entry mediator.