Figure 3.

Role of peripheral self-antigen in Treg homeostasis – 2 decades of progress. (i) Early experiments (1989) in fetal lambs showed that the continued presence of the thyroid gland was necessary for maintenance of immunological tolerance toward this organ. The cell type mediating such tolerance was not defined. (ii) Studies in the rat (1999) showed that ablation of the thyroid gland compromised the ability of peripheral CD4⁺ T cells to regulate autoimmune thyroiditis. (iii) Experiments in mice (2003, 2004, 2009) showed that Tregs proliferate in response to tissue-expressed self-antigen; Tregs isolated from draining LNs had a heightened capacity to regulate autoimmune organ destruction in a manner that was lost upon organ ablation.