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Affinity for self antigen selects Treg cells with distinct functional properties.

Lena Wyss1,2, Brian D Stadinski3, Carolyn G King1

  • 1Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.

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Summary

Regulatory T cells (Treg cells) have distinct subsets controlling immune responses. Highly self-reactive Treg cells manage lymph node proliferation, while less self-reactive ones prevent colitis by promoting induced Treg cell development.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Regulatory T cells (Treg cells) are crucial for maintaining lymphocyte homeostasis.
  • The specific mechanisms by which Treg cells exert control over immune responses are not fully elucidated.

Purpose of the Study:

  • To identify and characterize distinct Treg cell populations based on their self-reactivity and regulatory functions.
  • To understand the role of different Treg cell subsets in controlling lymphoproliferation and preventing autoimmune diseases like colitis.

Main Methods:

  • Identification of Treg cell subsets using surface markers (GITR, PD-1, CD25).
  • Assessment of Treg cell self-reactivity and functional assays in vitro and in vivo.
  • Analysis of Treg cell function in Foxp3-deficient (Scurfy) mouse models.

Main Results:

  • Two distinct Treg cell populations were identified: GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) and GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)).
  • Triple(hi) Treg cells are highly self-reactive and control lymphoproliferation in peripheral lymph nodes.
  • Triple(lo) Treg cells are less self-reactive and limit colitis by promoting CD4(+) Tconv cell conversion to induced Treg cells (iTreg cells).
  • Scurfy mice, lacking Treg cells, showed distinct phenotypes for Triple(hi)-like and Triple(lo)-like CD4(+) T cells, with the latter inducing colitis.

Conclusions:

  • Treg cell differentiation into distinct subsets is driven by T cell receptor affinity for self-antigen.
  • These Treg cell subsets possess non-overlapping regulatory activities crucial for immune homeostasis and prevention of autoimmunity.