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. 2019 Aug 20;8(8):939. doi: 10.3390/cells8080939

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Upon antigen stimulation, central Treg (cTreg) cells (CD62L^hi CCR7^hi CD44^lo) differentiate into effector Treg (eTreg) cells (CD62L^lo CCR7^lo CD44^hi) depending on TCR and CD28 signaling. After activation, TCR-dependent transcription factors, such as interferon regulatory factor 4 (IRF4), are induced and regulate the eTreg transcriptional program. In contrast, Foxo1 is inactivated by Akt-signaling, which decreases expression of cTreg-related molecules. Loss of Id2, transcription factor 1 (TCF1), and lymphoid enhancer binding factor 1 (LEF1) expression is a signature of mature eTreg cells. Mature eTreg cells highly express immune suppressive molecules, such as cytotoxic T cell antigen 4 (CTLA4) and inducible T cell costimulator (ICOS).