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. Author manuscript; available in PMC: 2025 Jan 1.
Published in final edited form as: J Allergy Clin Immunol. 2023 Sep 29;153(1):28–41. doi: 10.1016/j.jaci.2023.09.025

Figure 2. Developmental trajectory and subsets of regulatory T cells.

Figure 2

The regulatory T cell pool is composed of two major populations that act in concert to maintain peripheral tolerance. Natural regulatory T (nTreg) cells develop in the thymus and play a critical role in the maintenance of tolerance to self-antigens. Peripheral regulatory T (pTreg) cells are generated from conventional naïve CD4+ T cells at mucosal interfaces and barrier sites and are critically important for the maintenance of tolerance towards dietary, environmental and commensal antigens. Regulatory T cells can also be induced (iTreg) in-vitro from conventional naïve CD4+ T cells following TCR ligation in the presence of transforming growth factor beta (TGF-β). Although all three populations express high levels of the transcription factor Foxp3 and share the expression of several canonical Treg cell surface molecules including CTLA-4, CD25 and GITR, the TCR repertoires of nTreg and pTreg/iTreg and are distinct and non-overlapping. Although not uniquely expressed by nTreg cells, the Ikaros family transcription factor Helios and cell surface glycoprotein neuropilin-1 (Nrp-1) are highly expressed in nTreg as opposed to pTreg/iTreg populations. pTreg/iTreg cells exhibit a greater susceptibility towards destabilization and loss of Foxp3 expression, largely due to the absence of an nTreg-like specific demethylation signature at conserved non-coding sequences within the locus of Foxp3 and other Treg signature genes.