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Publication : Helios<sup>+</sup> and Helios<sup>-</sup> Treg subpopulations are phenotypically and functionally distinct and express dissimilar TCR repertoires.

First Author  Thornton AM Year  2019
Journal  Eur J Immunol Volume  49
Issue  3 Pages  398-412
PubMed ID  30620397 Mgi Jnum  J:274019
Mgi Id  MGI:6283208 Doi  10.1002/eji.201847935
Citation  Thornton AM, et al. (2019) Helios(+) and Helios(-) Treg subpopulations are phenotypically and functionally distinct and express dissimilar TCR repertoires. Eur J Immunol 49(3):398-412
abstractText  The transcription factor Helios is expressed in a large subset of Foxp3(+) Tregs. We previously proposed that Helios is a marker of thymic derived Treg (tTreg), while Helios(-) Treg were induced from Foxp3(-) T conventional (Tconv) cells in the periphery (pTreg). To compare the two Treg subpopulations, we generated Helios-GFP reporter mice and crossed them to Foxp3-RFP reporter mice. The Helios(+) Treg population expressed a more activated phenotype, had a slightly higher suppressive capacity in vitro and expressed a more highly demethylated TSDR but were equivalent in their ability to suppress inflammatory bowel disease in vivo. However, Helios(+) Treg more effectively inhibited the proliferation of activated, autoreactive splenocytes from scurfy mice. When Helios(+) and Helios(-) Treg were transferred to lymphoreplete mice, both populations maintained comparable Foxp3 expression, but Foxp3 expression was less stable in Helios(-) Treg when transferred to lymphopenic mice. Gene expression profiling demonstrated a large number of differentially expressed genes and showed that Helios(-) Treg expressed certain genes normally expressed in CD4(+) Foxp3(-) T cells. TCR repertoire analysis indicated very little overlap between Helios(+) and Helios(-) Treg. Thus, Helios(+) and Helios(-) Treg subpopulations are phenotypically and functionally distinct and express dissimilar TCR repertoires.
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