Neonatal thymectomy reveals differentiation and plasticity within human naive T cells
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
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
View: Text | PDF
Research Article Immunology

Neonatal thymectomy reveals differentiation and plasticity within human naive T cells

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

×

Figure 4

IL-8 production is enriched in the PTK7+ fraction of CD31+ naive CD4+ T cells and lost after cell division.

Options: View larger image (or click on image) Download as PowerPoint
IL-8 production is enriched in the PTK7+ fraction of CD31+ naive CD4+ T ...
(A) Proportion of CD31+ and CD31– naive CD4+ T cells in the CD4+ T cell compartment of HCs, 1–5 yr (n = 19) and Tx patients, 1–5 yr (n = 15). (B) Expression of IL-8 by CD31+ and CD31– naive CD4+ T cells of young HCs (n = 19) and Tx patients (n = 15). (C) Expression of IL-8 by CD31+ and CD31– naive CD4+ T cells of older HCs (n = 10) and older Tx patients separated on the basis of low (n = 7) or high percentage of CD31+ (n = 19). (D) Paired IL-8 expression measurements by SP CD3hiCD4+CD8– thymocytes and blood CD31+ naive CD4+ T cells (PBMCs) from the Tx neonates (n = 3). (E) IL-8 expression by PTK7+ (black dots) and PTK7– (gray dots) CD31+ naive CD4+ T cells from young HCs (n = 5). (F) PTK7 expression after each cell division following cytokine stimulation of FACS-sorted CD31+ naive CD4+ T cells from older HCs (n = 6). (G) IL-8 expression after each cell division following cytokine stimulation of FACS-sorted CD31+ naive CD4+ T cells from older HCs (n = 6). Data are shown as mean ± SD. See also Supplemental Figures 4 and 5. *P < 0.05, Mann-Whitney U test for unpaired data and Wilcoxon’s signed rank test for paired data.