Table 1.

Experimental evidence supporting a role for Notch signalling in mature T cell function.

	disease model	in vivo, loss-of-function strategy	outcome	citation
host defence	Trypanosoma cruzi infection	deletion of Notch2 in CD4+ T cells	impaired survival; impaired GZMB expression	[45]
	mycobacteria-elicited pulmonary granulomatosis	systemic anti-Dll4 treatment	larger granulomas; decreased Th17 cytokines (IL-17/17A/F, -6, -21)	[46]
	Leishmania major infection	deletion of Notch1 and Notch2 in T cells	susceptibility to infection, impaired IFNγ	[47]
	Influenza infection	deletion of Notch1 and Notch2 in CD8+ T cells; systemic anti-Dll1 treatment; GSI treatment	impaired viral clearance; decreased terminal effector cell differentiation, impaired IFNγ; impaired survival	[48,49]
	Listeria monocytogenes infection	deletion of Notch1 and Notch2 in CD8+ T cells	decreased short-term effector cell differentiation, impaired IFNγ	[50]
	Cryptococcus neoformans infection	DNMAML expression in T cells	increased fungal burden, impaired Th1/Th2 response	[51]
autoimmunity	experimental autoimmune encephalomyelitis (multiple sclerosis)	GSI treatment; systemic anti-Dll4 treatment; systemic anti-Notch3 treatment; DNMAML expression in T cells	decreased disease scores, impaired IFNγ; impaired IL-17A/IFNγ in CNS	[52–57]
alloimmunity	graft-versus-host disease	DNMAML expression in donor T cells; deletion of Notch1 and Notch2 or Rbpj in donor T cells; systemic anti-Notch1/2 or anti-Dll1/4 treatment; deletion of Dll1/4 in recipient CCL19+ stromal cells	decreased GVHD severity scores, increased survival, impaired IFNγ, increased Treg expansion	[58–66]
	heart transplant	systemic anti-Dll1 treatment + CTLA4-Ig/CD28KO; systemic anti-Dll1/4 treatment; DNMAML expression in T cells; systemic anti-Notch1 ± CTLA4-Ig treatment; Deletion of Notch1 in Tregs	delayed cardiac allograft rejection, impaired GZMB; impaired IFNγ/IL-4, decreased graft infiltration, decreased donor-specific alloantibodies	[67–69]
	lung transplant	systemic anti-Notch1 + anti-CLTA4-Ig treatment	preserved airway patency with less lymphocytic infiltrations and delayed lung allograft rejection	[69]
	human skin graft to mouse with chimeric human haematopoietic system	systemic anti-Notch1	decreased T cell infiltration, greater proportion of Tregs infiltrating, improved vascularity	[69]
model antigens	H-Y antigen	deletion of Dll4 in DCs	impaired CD4+ T cell activation and IL-2 production	[70]
	keyhole limpet Haemocyanin alum, Schistosoma mansoni egg extract	deletion of Notch1 and Notch2 or Rbpj in T cells	impaired CD4+ T cell activation	[71]