Reevaluation of T Cell Receptor Excision Circles as a Measure of Human Recent Thymic Emigrants

The human thymus exports newly generated T cells to the periphery. As no markers have been identified for these recent thymic emigrants (RTE), it is presently impossible to measure human thymic output. T cell receptor excision circles (TREC) have been recently used to assess thymic output during both health and disease. Using a mathematical model, we quantify age-dependent changes both in the number of RTE generated per day and in TREC concentration during an 80-year lifespan. Through analyses, we demonstrate that RTE and peripheral T cell division have the same potential to affect TREC concentration at any age in healthy people. T cell death also influences TREC concentration, but to a lesser extent. During aging, our results indicate that thymic involution primarily induces an age-dependent decline in TREC concentrations within both CD4+ and CD8+ T cell populations. We further apply this model for studying TREC concentration during HIV-1 infection. Our analyses reveal that a decrease in thymic output is the major contributor to the decline in TREC concentration within CD4+ T cells, whereas both increased peripheral T cell division and decreased thymic output induce the decline in TREC concentration within CD8+ T cells. Therefore, we suggest that T cell turnover should be examined together with TREC concentration as a measure of RTE. If peripheral T cell division remains relatively unchanged, then TREC concentration indeed reflects thymic output.This work was supported by National Institutes of Health Grant HL62119 (to D.E.K.) and Elizabeth Glaser Pediatric AIDS Foundation Student Intern Award (to P.Y.).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83366/1/ye-jimmunol-2002.pd