Table 2.

Strategies for targeting T regulatory cells (Tregs) and/or their function.

Impact on Tregs	Target	Drug	Rationale	Expected Treg depletion/blockade	Reference	Potential complications
Depletion	CD25	IL-2 immunotoxin	Treg targeting through attachment to CD25, the receptor for IL-2Treg killing through eEF-2 (Eukaryotic elongation factor 2) ribosylation by diphtheria toxin	Up to 75% depletion of circulating TregsUp to 40% depletion of the lymph node (LN) Tregs	(158, 167, 168)	Autoimmunity, toxicity
		Daclizumab	Binds to CD25, preventing IL-2 binding and action. Il-2 is required for maintenance of Treg counts and function	Up to 50% depletion of circulating Tregs	(169–172)
	CCR4	CCR4 immunotoxin	Targets Tregs by attaching to CCR4 (effector Treg marker) Treg killing through eEF-2 ribosylation by diphtheria toxin	Up to 40% depletion of circulating Tregs9–22% depletion of the LN Tregs	(173, 174)
		Mogalizumab	Targeting Tregs by attaching to CCR4 and causing antibody-dependent, cell-mediated cytotoxicity	Up to 80% depletion of circulating Tregs	(175, 176)
		Cyclophosphamide	Treg depletion through DNA double strand breaks and decreased DNA repair. Treg sensitivity is due to decreased production of glutathione (required for detoxification of Cy active metabolites)	Up to 50% depletion of circulating TregsIncreased CD8+ T cell and NK cell activation	(177, 178)
Functional blockade	CTLA-4	Ipilimumab	Binds to CTLA-4 on Tregs, blocking it from inhibiting lymphocytes	Up to 75% decrease of circulating Tregs	(100, 154, 179, 180)	Autoimmunity, toxicity
	IDO	1-methyl-d-tryptophan	Inhibits IDO, blocking suppressive function	Increased expression of IFN-γ by the lymphocytes in the LNs, decreased plasma viral loads	(181, 182)	Autoimmunity