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. 2023 Apr 27;13:1157345. doi: 10.3389/fonc.2023.1157345

Figure 1.

Figure 1

Phenotype and development of Tregs. (A) There are three Treg subtypes according to the sites of development: tTregs are developed in the thymus from the precursors of CD4+ T cells; pTregs are differentiated from mature CD4+ Th cells in the periphery upon encounter with antigens and other factors (IL-2, TGF-β, and retinoic acid); iTregs are developed from naïve T cells and require antigen stimulation in the presence of TGF-β and IL-2. (B) Development of cTregs and eTregs: tTregs migrate to peripheral lymphoid organs after thymus development and become cTregs, maintaining a naïve phenotype in the presence of IL-2 (CD45RA+, FOXP3lo, CD62L+, CCR7+). When cTregs and pTregs encounter TCR stimulation, they further differentiate into eTregs with expression of activation molecules CD44 and CTLA4. eTregs migrate and localize to non-lymphoid peripheral sites in response to specific stimuli. (C) Subfractions of human FOXP3+ Tregs: Fr. 1, CD45RA+ FOXP3lo CD25++ naïve Tregs; when naïve Tregs engage with antigens, they differentiate into Fr. 2 eTregs (CD45RA- FOXP3hi CD25+++); Fr. 3, non-Tregs, defined by CD45RA- FOXP3lo CD25++ cells.