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Blood, 28 May 2009, Vol. 113, No. 22, pp. 5480-5487.
Prepublished online as a Blood First Edition Paper on January 28, 2009; DOI 10.1182/blood-2008-10-184184.


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IMMUNOBIOLOGY

Quantifying the development of the peripheral naive CD4+ T-cell pool in humans

Iren Bains1,2, Rustom Antia3, Robin Callard1, and Andrew J. Yates3

1 Immunobiology Unit, Institute of Child Health, London, United Kingdom; 2 Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, London, United Kingdom; and 3 Department of Biology, Emory University, Atlanta, GA

What are the rules that govern a naive T cell's prospects for survival or division after export from the thymus into the periphery? To help address these questions, we combine data from existing studies with robust mathematical models to estimate the absolute contributions of thymopoiesis, peripheral division, and loss or differentiation to the human naive CD4+ T-cell pool between the ages of 0 and 20 years. Despite their decline in frequency in the blood, total body numbers of naive CD4+ T cells increase throughout childhood and early adulthood. Our analysis shows that postthymic proliferation contributes more than double the number of cells entering the pool each day from the thymus. This ratio is preserved with age; as the thymus involutes, the average time between naive T-cell divisions in the periphery lengthens. We also show that the expected residence time of naive T cells increases with time. The naive CD4+ T-cell population thus becomes progressively less dynamic with age. Together with other studies, our results suggest a complex picture of naive T-cell homeostasis in which population size, time since export from the thymus, or time since the last division can influence a cell's prospects for survival or further divisions.


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Related Article in Blood Online:

Be fruitful, multiply, and replenish
José A. M. Borghans and Kiki Tesselaar
Blood 2009 113: 5369-5370. [Full Text] [PDF]



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J. Immunol.Home page
I. Bains, R. Thiebaut, A. J. Yates, and R. Callard
Quantifying Thymic Export: Combining Models of Naive T Cell Proliferation and TCR Excision Circle Dynamics Gives an Explicit Measure of Thymic Output
J. Immunol., October 1, 2009; 183(7): 4329 - 4336.
[Abstract] [Full Text] [PDF]


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J. A. M. Borghans and K. Tesselaar
Be fruitful, multiply, and replenish
Blood, May 28, 2009; 113(22): 5369 - 5370.
[Full Text] [PDF]



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