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*Immunobiology Unit, Institute of Child Health, London, United Kingdom;
Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, London, United Kingdom;
INSERM U897 Epidemiology and Biostatistics, Institut de Santé Publique, d'Epidemiologie et de Développement, Université Victor Segalen Bordeaux 2, Bordeaux, France; and
Department of Biology, Emory University, Atlanta, GA 30322
Understanding T cell homeostasis requires knowledge of the export rate of new T cells from the thymus, a rate that has been surprisingly difficult to estimate. TCR excision circle (TREC) content has been used as a proxy for thymic export, but this quantity is influenced by cell division and loss of naive T cells and is not a direct measure of thymic export. We present in this study a method for quantifying thymic export in humans by combining two simple mathematical models. One uses Ki67 data to calculate the rate of peripheral naive T cell production, whereas the other tracks the dynamics of TRECs. Combining these models allows the contributions of the thymus and cell division to the daily production rate of T cells to be disentangled. The method is illustrated with published data on Ki67 expression and TRECs within naive CD4+ T cells in healthy individuals. We obtain a quantitative estimate for thymic export as a function of age from birth to 20 years. The export rate of T cells from the thymus follows three distinct phases, as follows: an increase from birth to a peak at 1 year, followed by rapid involution until 
8 years, and then a more gradual decline until 20 years. The rate of involution shown by our model is compatible with independent estimates of thymic function predicted by thymic epithelial space. Our method allows nonintrusive estimation of thymic output on an individual basis and may provide a means of assessing the role of the thymus in diseases such as HIV.
2 Address correspondence and reprint requests to Dr. Iren Bains, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom. E-mail address: i.bains{at}ucl.ac.uk
1 I.B. was supported by an Engineering and Physical Sciences Research Council Life Sciences Interface Doctoral Training Centre studentship. R.T. was supported by a grant from the Agence Nationale de Recherches sur le SIDA. A.J.Y. was supported by the National Institutes of Health.
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