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Thymic regulatory T cells arise via two distinct developmental programs.

David L Owen1, Shawn A Mahmud1, Louisa E Sjaastad1

  • 1Center for Immunology, Masonic Cancer Center, and the Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.

Nature Immunology
|January 16, 2019
PubMed
Summary
This summary is machine-generated.

Mature regulatory T cells (Treg cells) develop via two distinct pathways involving CD25+ and Foxp3lo progenitors. These distinct Treg cell developmental programs are crucial for establishing immune tolerance and preventing autoimmune diseases.

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Area of Science:

  • Immunology
  • Developmental Biology
  • Cell Biology

Background:

  • The generation of diverse regulatory T cell (Treg) repertoires capable of responding to self and non-self antigens is not fully understood.
  • Regulatory T cells are critical for maintaining immune homeostasis and preventing autoimmunity.

Purpose of the Study:

  • To elucidate the distinct developmental programs underlying the generation of mature regulatory T cell repertoires.
  • To investigate the functional differences between Treg cell subsets originating from distinct developmental pathways.

Main Methods:

  • Transcriptomic analysis
  • Histocytometry
  • Apoptosis assays
  • T cell receptor repertoire analysis
  • Experimental autoimmune encephalitis model

Main Results:

  • Two distinct Treg cell progenitor populations, CD25+ TregP and Foxp3lo TregP cells, were identified.
  • CD25+ TregP cells exhibited higher apoptosis rates and affinity for self-antigens, with distinct TCR repertoires and transcriptomes compared to Foxp3lo TregP cells.
  • Distinct signaling pathways and enhancers regulated the development of each progenitor type, suggesting co-option of negative and positive selection programs.
  • Treg cells derived from CD25+ TregP cells, but not Foxp3lo TregP cells, conferred protection against experimental autoimmune encephalitis.

Conclusions:

  • Mature Treg cells are generated through at least two distinct developmental programs.
  • Both developmental pathways are essential for a comprehensive Treg cell repertoire necessary for establishing immunotolerance.
  • Understanding these distinct Treg cell developmental programs offers insights into potential therapeutic strategies for autoimmune diseases.