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¹ The Biomedical Research Centre, ² Department of Medical Genetics, ³ Department of Chemistry, and ⁴ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada

CORRESPONDENCE Hermann J. Ziltener: hermann{at}brc.ubc.ca

Thymic T cell progenitor (TCP) importation is a periodic, gated event that is dependent on the expression of functional P-selectin ligands on TCPs. Occupancy of intrathymic TCP niches is believed to negatively regulate TCP importation, but the nature of this feedback mechanism is not yet resolved. We show that P-selectin and CCL25 are periodically expressed in the thymus and are essential parts of the thymic gate-keeping mechanism. Periodicity of thymic TCP receptivity and the size of the earliest intrathymic TCP pool were dependent on the presence of functional P-selectin ligand on TCPs. Furthermore, we show that the numbers of peripheral blood lymphocytes directly affected thymic P-selectin expression and TCP receptivity. We identified sphingosine-1-phosphate (S1P) as one feedback signal that could mediate influence of the peripheral lymphocyte pool on thymic TCP receptivity. Our findings suggest a model whereby thymic TCP importation is controlled by both early thymic niche occupancy and the peripheral lymphocyte pool via S1P.

Abbreviations used: ATF, activating transcription factor; C2GnT1, core 2 β1,6-glucosaminyltransferase-I; DOP, 2-deoxypyridoxine; DP, double positive; ETP, early TCP; HDL, high-density lipoprotein; ICAM-1, intercellular adhesion molecule 1; LC-MS/MS, liquid chromatography–mass spectrometry/mass spectrometry; PSGL-1, P-selectin glycoprotein ligand 1; qrtPCR, quantitative real-time PCR; S1P, sphingosine-1-phosphate; S1PR, S1P receptor; SP, single positive; TCP, T cell progenitor; TREC, T cell receptor excision circle; TN, triple negative; VCAM-1, vascular cell adhesion molecule 1; VE-cadherin, vascular endothelial–cadherin.

© 2009 Gossens et al
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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