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Identification of a human recent thymic emigrant phenotype
R D McFarland1, D C Douek, R A Koup
1Division of Hematopathology and Immunology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Summary
Measuring recent thymic emigrants (RTE) is crucial for understanding T cell immunity. A new phenotypic approach using alphaE integrin (CD103) on naive CD8+ T cells offers a reliable method to estimate thymic function.
Area of Science:
- Immunology
- T cell biology
- Developmental immunology
Background:
- Measuring human thymic output is vital for studying T cell repertoire development and regeneration after therapies.
- Quantifying T cell receptor rearrangement excision circles (TREC) has been used to assess recent thymic emigrants (RTE), but is complicated by T cell turnover.
- A reliable method to measure thymic function and recent thymic emigrants is needed.
Purpose of the Study:
- To develop and validate a phenotypic approach for measuring recent thymic emigrants (RTE).
- To identify a specific cell surface marker that defines RTE in peripheral blood.
- To assess the utility of this marker in estimating ongoing thymopoiesis.
Main Methods:
- Investigated alphaE integrin (CD103) expression on thymocytes and peripheral T cells.
- Phenotypically characterized CD103+ naive CD8+ T cells using markers like CD45RO, CD62L, CD27, CD11a, and CD95.
- Quantified T cell receptor rearrangement excision circles (TREC) in sorted CD103+ and CD103- naive CD8+ T cell populations.
- Examined the effect of age and thymectomy on the frequency of CD103+ naive CD8+ T cells.
Main Results:
- CD103 is up-regulated late in thymic development and identifies a distinct subset of naive CD8+ T cells in the periphery.
- The CD103+ naive CD8+ T cell subset exhibits a naive phenotype and high TREC levels, differentiating it from memory T cells.
- Sorted CD103+ naive CD8+ T cells have higher TREC levels than CD103- counterparts.
- The frequency of this CD103+ subset declines with age and is significantly reduced by thymectomy.
Conclusions:
- CD103 expression defines a population of recent thymic emigrants (RTE) within naive CD8+ T cells.
- Quantification of CD103+ naive CD8+ T cells in peripheral blood provides a reliable estimate of ongoing thymopoiesis.
- This phenotypic approach offers a valuable tool for assessing thymic function in various clinical contexts.