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Unstable regulatory T cells, enriched for naive and Nrp1(neg) cells, are purged after fate challenge

Authors
  • Junius, Steffie; 111889;
  • Mavrogiannis, Adamantios; 134001;
  • Lemaitre, Pierre;
  • Gerbaux, Margaux; 135658;
  • Staels, Frederik; 125776;
  • Malviya, Vanshika; 131998;
  • Burton, Oliver;
  • Gergelits, Vaclav;
  • Singh, Kailash;
  • Tadeo, Raul Yhossef Tito;
  • Raes, Jeroen; 39804;
  • Humblet-Baron, Stephanie; 75170;
  • Liston, Adrian; 61929;
  • Schlenner, Susan M; 84381;
Publication Date
Jul 01, 2021
Source
Lirias
Keywords
License
Unknown
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Abstract

Regulatory T cells (Tregs) are indispensable for the control of immune homeostasis and have clinical potential as a cell therapy for treating autoimmunity. Tregs can lose expression of the lineage-defining Foxp3 transcription factor and acquire effector T cell (Teff) characteristics, a process referred to as Treg plasticity. The extent and reversibility of such plasticity during immune responses remain unknown. Here, using a murine genetic fate-mapping system, we show that Treg stability is maintained even during exposure to a complex microbial/antigenic environment. Furthermore, we demonstrate that the observed plasticity of Tregs after adoptive transfer into a lymphopenic environment is a property limited to only a subset of the Treg population, with the nonconverting majority of Tregs being resistant to plasticity upon secondary stability challenge. The unstable Treg fraction is a complex mixture of phenotypically distinct Tregs, enriched for naïve and neuropilin-1-negative Tregs, and includes peripherally induced Tregs and recent thymic emigrant Tregs These results suggest that a "purging" process can be used to purify stable Tregs that are capable of robust fate retention, with potential implications for improving cell transfer therapy. / status: published

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