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Neonatal thymectomy reveals differentiation and plasticity within human naive T cells
Theo van den Broek, … , Nicolaas J.G. Jansen, Femke van Wijk
Theo van den Broek, … , Nicolaas J.G. Jansen, Femke van Wijk
Published February 22, 2016
Citation Information: J Clin Invest. 2016;126(3):1126-1136. https://doi.org/10.1172/JCI84997.
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Research Article Immunology

Neonatal thymectomy reveals differentiation and plasticity within human naive T cells

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Abstract

The generation of naive T cells is dependent on thymic output, but in adults, the naive T cell pool is primarily maintained by peripheral proliferation. Naive T cells have long been regarded as relatively quiescent cells; however, it was recently shown that IL-8 production is a signatory effector function of naive T cells, at least in newborns. How this functional signature relates to naive T cell dynamics and aging is unknown. Using a cohort of children and adolescents who underwent neonatal thymectomy, we demonstrate that the naive CD4+ T cell compartment in healthy humans is functionally heterogeneous and that this functional diversity is lost after neonatal thymectomy. Thymic tissue regeneration later in life resulted in functional restoration of the naive T cell compartment, implicating the thymus as having functional regenerative capacity. Together, these data shed further light on functional differentiation within the naive T cell compartment and the importance of the thymus in human naive T cell homeostasis and premature aging. In addition, these results affect and alter our current understanding on the identification of truly naive T cells and recent thymic emigrants.

Authors

Theo van den Broek, Eveline M. Delemarre, Willemijn J.M. Janssen, Rutger A.J. Nievelstein, Jasper C. Broen, Kiki Tesselaar, Jose A.M. Borghans, Edward E.S. Nieuwenhuis, Berent J. Prakken, Michal Mokry, Nicolaas J.G. Jansen, Femke van Wijk

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Figure 3

Naive CD4+ T cell functionality is impaired after neonatal thymectomy in early life, but restores after thymic regeneration in later life.

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Naive CD4+ T cell functionality is impaired after neonatal thymectomy in...
(A) Left panel, calcium flux of CD4+ naive T cells in young children (young HCs, n = 4 black, young Tx, n = 6 gray, mean ± SD). Right panel, AUC of the calcium flux. (B) Representative dot plot of IL-8 production in CD45RA+CD4+ T cell population of young HCs. (C) IL-2 production in naive CD4+ T cells of young HCs (n = 15) and young Tx patients (n = 10) after PMA/ion stimulation. (D) IL-8 production by naive CD4+ T cells of young HC (n = 19) and young Tx patient (n = 15) PMA/ion stimulation. (E) Left panel, calcium flux of CD4 naive T cells of older HCs and Tx children. Right panel, AUC of the calcium flux (HC 1–5 yr, n = 5; high CD31, Tx > 10 yr, n = 6; low CD31, Tx > 10 yr, n = 1). (F) IL-8 production in naive CD4+ T cells of older HC (n = 10) and Tx patient (high CD31, n = 17; low CD31, n = 7) PMA/ion stimulation. Data are shown as mean ± SD. See also Supplemental Figure 3. *P < 0.05, Mann-Whitney U test.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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