Fig. E3.1. Schematic depiction of autoimmunity by design in the absence (A) or the presence (B) of autoimmune disease. (A) Naïve autoreactive T cell precursors emerge from the thymus and differentiate into regulatory T cells. These regulatory T cells interact with quiescent or immature antigen-presenting cells (APCs) and normal parenchymal cells to create a protective microenvironment. This interactive process prevents activation and effector function of any potentially pathogenic autoreactive T cells. (B) Under unusual proinflammatory conditions pathogenic, autoreactive T cells expand in a proinflammatory microenvironment (comprised of activated APCs, chemoattractant signals, and the absence of protective signals) to an extent that cannot be controlled by regulatory cells and results in autoimmune disease.

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