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Updated: Jun 30, 2026
14:29
Examination of Thymic Positive and Negative Selection by Flow Cytometry
Published on: October 8, 2012
TCR signal strength during positive selection shapes CD25 expression patterns on thymically derived regulatory T
1University of California, Berkeley, Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, Berkeley, CA.
Biorxiv : the Preprint Server for Biology
|June 29, 2026
Summary
The strength of T cell receptor signals during thymic selection influences regulatory T cell (Treg) development. Weak selection signals can lead to Tregs lacking CD25, an alternative Treg lineage.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Regulatory T cells (Tregs) are crucial for maintaining immune homeostasis.
- Tregs primarily develop in the thymus, but the impact of thymic selection on their peripheral function is not fully understood.
Purpose of the Study:
- To investigate how the strength of T cell receptor (TCR) signaling during positive selection in the thymus affects the differentiation and characteristics of CD4 T cells.
- To determine the impact of thymic selection on the development of peripheral regulatory T cells.
Main Methods:
- Analysis of CD4 SP thymocytes based on CD5 expression levels (indicating TCR signal strength during positive selection).
- Assessment of Foxp3+ cell production and CD25 expression.
- In vitro Treg induction assays using TGFβ and IL-2.
Main Results:
- Thymocytes experiencing weak positive selection signals (CD5LO CD4 SP) produced Foxp3+ cells lacking CD25.
- These CD25-negative Tregs showed a greater dependency on TGFβ than IL-2 for induction.
- CD4 clones generating CD25- thymic Tregs also produced CD25- peripheral Tregs.
Conclusions:
- Positive selection in the thymus critically influences how CD4 T cells respond to TCR and cytokine signals.
- An alternative lineage of Tregs, characterized by the absence of constitutive CD25 expression, can arise from thymocytes that underwent weak positive selection.
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