Measuring Emigration of Human Thymocytes by T-Cell Receptor Excision Circles

Abstract

Recent advances in characterizing thymic function confirm the importance of thymus to T-cell diversity in the periphery of both children and adults during both health and disease. Lack of a marker to identify human recent thymic emigrants (RTEs) is the biggest hurdle to accurately characterizing and quantifying thymic output. T-cell receptor excision circles (TRECs) are used as an assay to measure RTE levels. Controversy exists, however, as to whether TREC concentrations reflect the number of RTEs or are mainly altered by peripheral T-cell division and death. In this review, we first summarize recent data on the human thymus and RTEs. On the basis of both experimental and mathematical analyses, we characterize factors that influence TREC dynamics in the periphery and elucidate primary elements that induce a decline in TREC concentrations during normal aging and HIV-1 infection. Our findings suggest that T-cell dynamics are key to the accuracy of TREC concentrations as a useful measurement of human RTEs.