T cell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation

T cell differentiation in the thymus is characterized by a hierarchical ord er of rearrangement steps' in the T cell receptor (TCR) genes, resulting in the joining of V, D, and J gene segments. During each of the rearrangement steps, DNA fragments between rearranging V, D. and J gene segments are del eted as circular excision products, the so-called TRECs (T cell receptor ex cision circles). TRECs are assumed to have a high over-time stability, but they can not multiply and consequently are diluted during T cell proliferat ion. It was recently suggested that quantitative detection of TRECs would a llow for direct measurement of thymic output. The delta Rec-psiJ alpha TREC appears to be the best marker, because the majority of thymocyte expansion occurs before this TREC is formed. However, apart from thymic output sever al other factors determine the TREC content of a T cell population, such as cell division and cell death. Likewise, the number of TRECs depends not on ly on thymic output, but also on the longevity of naive T cells. This warra nts caution with regard to the interpretation of TREC data as measured in h ealthy and diseased individuals. delta Rec-psiJ alpha TREC detection is a n ew and elegant tool for identification of recent thymic emigrants in the pe riphery, but further research is required for making quantitative estimatio ns of thymic output with the use of TREC analysis.