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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3777-3785. Prepublished online as a Blood First Edition Paper on August 8, 2006; DOI 10.1182/blood-2006-02-004531. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-004531v1 108/12/3777    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gray, D. H. D. Articles by Boyd, R. L. Search for Related Content PubMed PubMed Citation Articles by Gray, D. H. D. Articles by Boyd, R. L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 17, 2006 Accepted July 24, 2006 Developmental kinetics, turnover and stimulatory capacity of thymic epithelial cells Daniel H. D. Gray, Natalie Seach, Tomoo Ueno, Morag K. Milton, Adrian Liston, Andrew M Lew, Christopher C. Goodnow, and Richard L. Boyd* Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Wellington Road, Australia Monash Immunology and Stem Cell Laboratories, Monash University John Curtin School of Medical Research, Australian National University Walter and Eliza Hall Institute * Corresponding author; email: richard.boyd{at}med.monash.edu.au. Despite the importance of thymic stromal cells to T-cell development, relatively little is known about their biology. Here we employ single-cell analysis of stromal cells to analyse extensive changes in the number and composition of thymic stroma throughout life, revealing a surprisingly dynamic population. Phenotypic progression of thymic epithelial subsets was assessed at high resolution in young mice to provide a developmental framework. The cellular and molecular requirements of adult epithelium were studied using various mutant mice to demonstrate new crosstalk checkpoints dependent on RelB in the cortex and CD40 in the medulla. Using Ki67 and BrdU labelling, the turnover of thymic epithelium was found to be rapid, but then diminished upon thymic involution. The various defects in stromal turnover and composition that accompanied involution were rapidly reversed following sex steroid ablation. Unexpectedly, mature cortical and medullary epithelium showed a potent capacity to stimulate naive T-cells, comparable to that of thymic dendritic cells. Overall, these studies show that the thymic stroma is a surprisingly dynamic population, and may have a more direct role in negative selection than previously thought. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The thymus: a house dividing Geoffrey O. Gillard and Andrew G. Farr Blood 2006 108: 3629-3630. [Full Text] [PDF] This article has been cited by other articles: R. M. Kelly, S. L. Highfill, A. Panoskaltsis-Mortari, P. A. Taylor, R. L. Boyd, G. A. Hollander, and B. R. Blazar Keratinocyte growth factor and androgen blockade work in concert to protect against conditioning regimen-induced thymic epithelial damage and enhance T-cell reconstitution after murine bone marrow transplantation Blood, June 15, 2008; 111(12): 5734 - 5744. [Abstract] [Full Text] [PDF] N. Seach, T. Ueno, A. L. Fletcher, T. Lowen, M. Mattesich, C. R. Engwerda, H. S. Scott, C. F. Ware, A. P. Chidgey, D. H. D. Gray, et al. The Lymphotoxin Pathway Regulates Aire-Independent Expression of Ectopic Genes and Chemokines in Thymic Stromal Cells J. Immunol., April 15, 2008; 180(8): 5384 - 5392. [Abstract] [Full Text] [PDF] D. Gray, J. Abramson, C. Benoist, and D. Mathis Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire J. Exp. Med., October 29, 2007; 204(11): 2521 - 2528. [Abstract] [Full Text] [PDF] J. Gui, X. Zhu, J. Dohkan, L. Cheng, P. F. Barnes, and D.-M. Su The aged thymus shows normal recruitment of lymphohematopoietic progenitors but has defects in thymic epithelial cells Int. Immunol., October 1, 2007; 19(10): 1201 - 1211. [Abstract] [Full Text] [PDF] V. P. Zediak, I. Maillard, and A. Bhandoola Multiple prethymic defects underlie age-related loss of T progenitor competence Blood, August 15, 2007; 110(4): 1161 - 1167. [Abstract] [Full Text] [PDF] S. W. Rossi, M.-Y. Kim, A. Leibbrandt, S. M. Parnell, W. E. Jenkinson, S. H. Glanville, F. M. McConnell, H. S. Scott, J. M. Penninger, E. J. Jenkinson, et al. RANK signals from CD4+3 inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla J. Exp. Med., June 11, 2007; 204(6): 1267 - 1272. [Abstract] [Full Text] [PDF] Y.-W. Chu and F. T. Hakim KGF boosts thymic archiTECture Blood, May 1, 2007; 109(9): 3613 - 3614. [Full Text] [PDF] S. W. Rossi, L. T. Jeker, T. Ueno, S. Kuse, M. P. Keller, S. Zuklys, A. V. Gudkov, Y. Takahama, W. Krenger, B. R. Blazar, et al. Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells Blood, May 1, 2007; 109(9): 3803 - 3811. [Abstract] [Full Text] [PDF] D. Min, A. Panoskaltsis-Mortari, M. Kuro-o, G. A. Hollander, B. R. Blazar, and K. I. Weinberg Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging Blood, March 15, 2007; 109(6): 2529 - 2537. [Abstract] [Full Text] [PDF] G. O. Gillard, J. Dooley, M. Erickson, L. Peltonen, and A. G. Farr Aire-Dependent Alterations in Medullary Thymic Epithelium Indicate a Role for Aire in Thymic Epithelial Differentiation J. Immunol., March 1, 2007; 178(5): 3007 - 3015. [Abstract] [Full Text] [PDF]

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