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Session 70 Poster Session Thymic Function and Immune Reconstitution Session Time: 4:30-6:30 pm Room 4E-F

506-M. Reevaluation of T-Cell Receptor Excision Circles as a Measure of Human Recent Thymic Emigrants P. Ye* and D. Kirschner Univ. of Michigan, Ann Arbor Background: 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 currently impossible to measure human thymic output. The T-cell receptor excision circle (TREC) assay has been recently developed to assess thymic output during both aging and HIV-1 infection. However, controversy exists as to whether TREC concentration is a good marker for RTEs, since TREC concentration is also affected by peripheral T-cell turnover. Methods: We developed a mathematical model that describes human thymopoiesis and sjTREC dynamics between the thymus and peripheral blood/lymphoid tissues. Results: Our model quantifies age-dependent changes in the number of RTEs produced per day and in TREC concentration over an 80-year lifespan. We demonstrate that TREC concentration is equally affected by recent thymic emigrants and peripheral T-cell division at any age. T-cell death also influences TREC concentration, but to a lesser extent. Our results further indicate that thymic involution primarily induces an age-dependent decline in TREC concentrations in both CD4+ and CD8+ T cell populations. During HIV-1 infection, our analyses reveal that decreased thymic output is the major contributor to the decline of TREC concentration in CD4+ T cells, while both increased peripheral T-cell division and decreased thymic output induce the decline of TREC concentration in CD8+ T cells. Conclusions: Our findings suggest that peripheral T-cell turnover should be examined together with TREC concentration as a measure of thymic output. If T-cell turnover remains relatively unchanged, TREC concentration could reflect thymic output.

©2002 9th Conference on Retroviruses and Opportunistic Infections