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Rare development of Foxp3+ thymocytes in the CD4+CD8+ subset
Hyang Mi Lee1, Chyi-Song Hsieh
1Department of Internal Medicine, Division of Rheumatology, Washington University, St Louis, MO 63110, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|July 22, 2009
Summary
Most regulatory T (Treg) cells do not develop at the double positive (DP) stage. Researchers found that Foxp3(+) DP cells are often artifacts, with Treg development occurring later in thymocyte maturation.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Natural regulatory T (Treg) cells are crucial for preventing autoimmunity.
- The double positive (DP) stage of thymic development was previously considered the earliest source of Treg cells.
Purpose of the Study:
- To re-evaluate the contribution of the DP stage to natural Treg cell generation.
- To clarify the actual developmental stages where Foxp3 expression is induced in thymocytes.
Main Methods:
- Flow cytometry analysis, including height and width parameters.
- Analysis of post-sort contaminants.
- Thymocyte mixing experiments.
- Neonatal bone marrow chimera studies to track Treg development temporally.
Main Results:
- Most Foxp3(+) DP cells identified by standard flow cytometry are artifacts (doublets).
- Actual Treg cell development is minimal at the DP stage.
- Treg cell generation primarily occurs at the immature HSA(high) CD4SP stage.
Conclusions:
- The double positive (DP) stage is not a major source of natural Foxp3(+) regulatory T cells.
- Efficient induction of Foxp3 likely requires further thymocyte maturation beyond the DP stage.
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