Images of self: a model for tonic peripheral tolerance.

A model for peripheral tolerance is proposed in which immune reactivity is controlled by the presence (cf. absence) of CD4+ T cells. Continuous 'tonic' recognition of self is maintained throughout adult life by, among others, a subset of 'autoreactive' CD4+ T cells recognizing 'dominant' determinants derived from self-antigens. It is hypothesized that these cells have survived intrathymic deletion to be tolerized in the periphery, where they continue to function by tolerizing other similarly reactive thymic emigrants. This 'image' of self is postulated to arise during fetal and early neonatal life, remaining largely invariant thereafter, and serves as the backdrop against which recognition of 'non-self' occurs. The model is discussed in the context of two examples of experimental autoimmune disease: induced autoimmunity in the 2-4 day old neonatally thymectomized mouse and spontaneous diabetes in the non-obese diabetic (NOD) mouse.