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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4715-4721. Prepublished online as a Blood First Edition Paper on February 24, 2005; DOI 10.1182/blood-2004-10-4051. This Article Full Text (PDF) All Versions of this Article: 2004-10-4051v1 105/12/4715    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 Darrasse-Jeze, G. Articles by Klatzmann, D. Search for Related Content PubMed PubMed Citation Articles by Darrasse-Jeze, G. Articles by Klatzmann, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 20, 2004 Accepted February 17, 2005 Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetus Guillaume Darrasse-Jeze, Gilles Marodon, Benoit L Salomon, Martin Catala, and David Klatzmann* Laboratoire de Biologie et Therapeutique des Pathologies Immunitaires, Universite Pierre et Marie Curie (UPMC) / Centre National de la Recherche Scientifique (CNRS), Unite Mixte de Recherche (UMR) 7087, Paris, France Departement de Genetique, Cytogenetique et Embryologie, UPMC/CNRS UMR 7000, Paris, France Laboratoire de Biologie et Therapeutique des Pathologies Immunitaires, Universite Pierre et Marie Curie (UPMC) / Centre National de la Recherche Scientifique (CNRS), Unite Mixte de Recherche (UMR) 7087, Paris, France; Service de Biotherapie, Hopital Pitie-Salpetriere, Paris, France * Corresponding author; email: david.klatzmann{at}chups.jussieu.fr. Little is known about the ontogeny of naturally occurring CD4+CD25+ regulatory/suppressor T cells that play a major role in maintaining self-tolerance in mouse and human. In rodents, thymectomy on day 3 of life leads to multiple organ specific autoimmune diseases that can be prevented by adoptive transfer of regulatory T cells, suggesting their neonatal development. We investigated regulatory T cell ontogeny in 11 human fetuses. Thymic CD4+CD25+ cells were detected as early as at 13 weeks of gestation, together with the first mature T cells. Thymic CD25+ cells appeared to be positively selected at the CD4+CD8+CD3hi differentiation stage, as assessed by CD1a and CD69 expression. The proportion of thymic CD4+CD25+ cells appeared quite stable with age, around 6-7%, similar to the proportion observed in infant thymus. Extra-thymic CD4+CD25+ T cells could hardly be detected at 13 weeks of gestation, but were present from week 14 onwards. As adult regulatory T cells, purified CD4+CD25+ fetal cells were anergic and suppressed T cell proliferative responses; they expressed intracellular CTLA4, and Foxp3-mRNA. Altogether, our results indicate that the generation of regulatory/suppressor T cells is consubstantial to the generation of a functional and self-tolerant immune system. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. A. Fernandez, F. K. Puttur, Y. M. Wang, W. Howden, S. I. Alexander, and C. A. Jones T Regulatory Cells Contribute to the Attenuated Primary CD8+ and CD4+ T Cell Responses to Herpes Simplex Virus Type 2 in Neonatal Mice J. Immunol., February 1, 2008; 180(3): 1556 - 1564. [Abstract] [Full Text] [PDF] D. J. Hartigan-O'Connor, K. Abel, and J. M. McCune Suppression of SIV-specific CD4+ T cells by infant but not adult macaque regulatory T cells: implications for SIV disease progression J. Exp. Med., October 29, 2007; 204(11): 2679 - 2692. [Abstract] [Full Text] [PDF] C. Hubeau, I. Apostolou, and L. Kobzik Targeting of CD25 and Glucocorticoid-Induced TNF Receptor Family-Related Gene-Expressing T Cells Differentially Modulates Asthma Risk in Offspring of Asthmatic and Normal Mother Mice J. Immunol., February 1, 2007; 178(3): 1477 - 1487. [Abstract] [Full Text] [PDF] B. Fritzsching, N. Oberle, E. Pauly, R. Geffers, J. Buer, J. Poschl, P. Krammer, O. Linderkamp, and E. Suri-Payer Naive regulatory T cells: a novel subpopulation defined by resistance toward CD95L-mediated cell death Blood, November 15, 2006; 108(10): 3371 - 3378. [Abstract] [Full Text] [PDF] W. Hansen, K. Loser, A. M. Westendorf, D. Bruder, S. Pfoertner, C. Siewert, J. Huehn, S. Beissert, and J. Buer G Protein-Coupled Receptor 83 Overexpression in Naive CD4+CD25- T Cells Leads to the Induction of Foxp3+ Regulatory T Cells In Vivo J. Immunol., July 1, 2006; 177(1): 209 - 215. [Abstract] [Full Text] [PDF] J. Michaelsson, J. E. Mold, J. M. McCune, and D. F. Nixon Regulation of T Cell Responses in the Developing Human Fetus J. Immunol., May 15, 2006; 176(10): 5741 - 5748. [Abstract] [Full Text] [PDF] D. A. Randolph The Neonatal Adaptive Immune System NeoReviews, October 1, 2005; 6(10): e454 - e462. [Full Text] [PDF]

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