Figure 1.

Conceptual parallels between the approach to autoimmunity and allergy tolerance trials, using examples from T1D and from peanut allergy. Identification of early at-risk children allows for prevention strategies that rely on antigen exposure in the context of immune deviation or anergy. After initial antigen sensitization, however, additional measures are required to blunt effector responses to inhibit immune amplification events. Failing this, determinant spreading elicits robust immunity that recruits additional effector pathways and conditions inflammatory innate tissue responses, now requiring combinations of targeted therapeutics to ‘reset’ the immunological threshold and enable an opportunity to reestablish homeostatic balance between regulatory and effector pathways. Recognition of these differences requires appropriate staging and monitoring in order to select therapeutic options with tolerogenic potential.