Quantifying thymic export: combining models of naive T cell proliferation and TCR excision circle dynamics gives an explicit measure of thymic output

Bains, I., Thiebaut, R., Yates, A. J. and Callard, R. (2009) Quantifying thymic export: combining models of naive T cell proliferation and TCR excision circle dynamics gives an explicit measure of thymic output. Journal of Immunology, 183(7), pp. 4329-4336. (doi:10.4049/jimmunol.0900743)

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Publisher's URL: http://dx.doi.org/10.4049/jimmunol.0900743

Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Yates, Professor Andrew
Authors: Bains, I., Thiebaut, R., Yates, A. J., and Callard, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Journal Abbr.:J. Immunol.
Publisher:American Association of Immunologists
ISSN:0022-1767
ISSN (Online):1550-6606

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