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Keywords:

  • regulatory T cell;
  • FOXP3;
  • TCR;
  • costimulation;
  • cytokines;
  • thymus;
  • peripheral tolerance

Natural regulatory T cells (nTregs) are defined by their inherent ability to establish and maintain peripheral self-tolerance. In recent years, the development of nTregs has come under close examination with the advent of Forkhead Box P3 protein (FOXP3)-green fluorescent protein reporter mice that pinpointed the initiation of FOXP3 expression within the thymus. The mechanism and pathway of nTreg development has only recently been studied in detail and to a large degree remains unclear. In this review, we will discuss our current understanding of nTreg lineage choice and development from a cellular and intracellular standpoint.