TABLE 1.

Mechanisms of action of antigen-specific immunotherapy and predicted nature of response

Mechanism	Predicted outcomes	Tolerance induction	Durability
Immune regulation induced against β-cell antigen (typically associated with aTregs, IL-10, TGF-β induction)	Responses should be detectable (e.g., by cytokine production or functional read-out)	Operational tolerance should be achieved	Responses durable in the range of months up to 1 year
	Should offer benefit of linked suppression of response to other β-cell antigens
Immune deviation associated with change of dominant cellular phenotype (e.g., from TH1 to TH2)	Responses should be detectable (e.g., by cytokine production or functional read-out)	Operational tolerance should be achieved	Responses durable in the range of months
	May offer benefit of linked suppression
Immune deletion of β-cell antigen-specific T-cells	Difficult to detect deletion	Operational tolerance not guaranteed	Transient (weeks/months)
	No benefit of linked suppression