Cutting edge: Hematopoietic-derived APCs select regulatory T cells in thymus

Area of Science:

• Immunology
• Cell Biology

Background:

• Regulatory T cells (Tregs) are crucial for immune tolerance.
• Treg development depends on self-peptide-MHC recognition by high-affinity TCRs and CD28 signaling.
• The specific antigen-presenting cells (APCs) involved in Treg selection remain unclear.

Purpose of the Study:

• To investigate the distinct roles of hematopoietic-derived APCs (HCs) and thymic epithelial cells (TECs) in Treg selection.
• To determine if CD28/B7 signaling in HCs or TECs is essential for Treg development.

Main Methods:

• Construction of bone marrow chimeras with disrupted CD28/B7 signaling in either HCs or TECs.
• Analysis of Treg generation within the thymus of these chimeras.

Main Results:

• Both HCs and TECs can independently and fully reconstitute the thymic Treg population.
• Treg selection necessitates TCR signaling and CD28 costimulation presented in cis on the same APC type.
• Hematopoietic cells play a previously unrecognized role in thymic Treg development.

Conclusions:

• Both HCs and TECs are essential and functionally redundant for Treg generation in the thymus.
• Co-localization of TCR and CD28 signals on a single APC is critical for Treg selection.
• This study identifies a novel role for HCs in Treg development.