FIG. 3.

Bystander suppression by Tregs: Tolerance tag team? When an APC presents β-cell proteins to an autoreactive Treg following, for example, mucosal immunization with insulin or subcutaneous immunization with GAD, autoreactive T-cells that recognize this protein, among them Tregs, become activated, proliferate, and circulate throughout the body. The activated cells will reach various organs and scan them for the antigentic protein, as shown to occur in the pancreatic draining lymph nodes and sometimes the islets in type 1 diabetes animal models. The number of cells is further augmented by proliferation within the lymph node or pancreatic islets, and soluble mediators secreted by the Tregs in these localized areas will now have multiple beneficial effects and mediate long-term tolerance by suppressing the aggressive autoreactive effector response.