Direct evidence for thymic function in adult humans.

Area of Science:

• Immunology
• Human Thymic Function
• T Cell Homeostasis

Background:

• Understanding thymic function is vital for T cell homeostasis.
• Quantifying recent thymic emigrants (RTEs) in humans is challenging.

Purpose of the Study:

• To develop a novel assay for quantifying RTE frequency and diversity in human peripheral blood.
• To define RTEs based on T cell receptor (TCR) rearrangement deletion circles (DCs).

Main Methods:

• Development of a novel assay to detect TCR deletion circles (DCs) as markers for RTEs.
• Analysis of T cells from thymus, cord blood, and adult peripheral blood (ages 22-76).
• Phenotypic characterization of RTEs in peripheral blood subpopulations (e.g., CD4+CD45RA+CD62L+).

Main Results:

• TCR DCs were detected in T cells from thymus, cord blood, and adult peripheral blood.
• RTEs were most frequent in naive T cells (CD4+CD45RA+CD62L+) but also present in other T cell subsets.
• RTEs exhibited multiple Vbeta rearrangements, indicating oligoclonal repertoire replenishment.

Conclusions:

• The novel assay effectively quantifies RTEs in human peripheral blood.
• The adult thymus continuously contributes a diverse repertoire of new T cells to circulation, even in older individuals.
• This finding has implications for understanding immune function and age-related immune changes.