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High- and low-affinity regulatory T cells (Tregs) protect against autoimmune diabetes. Different TCR affinities lead to distinct Treg functional profiles, suggesting nonredundant roles in controlling autoimmunity.

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Area of Science:

  • Immunology
  • Autoimmunity
  • T cell biology

Background:

  • Regulatory T cells (Tregs) possess a unique TCR repertoire and heightened self-reactivity compared to conventional T cells.
  • The precise role of TCR affinity in modulating the function of self-reactive Tregs remains largely uncharacterized.

Purpose of the Study:

  • To investigate the impact of TCR affinity on Treg function in the context of autoimmune diabetes using a two-TCR model.
  • To elucidate the distinct functional profiles of high- and low-affinity Tregs during autoimmune responses.

Main Methods:

  • Utilized a two-TCR model to simulate distinct TCR affinities in regulatory T cells.
  • Assessed Treg recruitment to the pancreas and evaluated the expression of key functional mediators.

Main Results:

  • Both high- and low-affinity Tregs were recruited to the pancreas and conferred protection against autoimmune diabetes.
  • High-affinity Tregs preferentially upregulated IL-10, TIGIT, GITR, and CTLA4.
  • Low-affinity Tregs showed increased expression of Areg and Ebi3, indicating divergent functional pathways.

Conclusions:

  • TCR affinity plays a critical role in shaping Treg function during autoimmunity.
  • Distinct functional profiles of high- and low-affinity Tregs suggest mechanistically separate and potentially nonredundant roles in controlling autoimmune diabetes.