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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 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 Citation Map 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-Jèze, G. Articles by Klatzmann, D. Search for Related Content PubMed PubMed Citation Articles by Darrasse-Jèze, G. Articles by Klatzmann, D. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetuses Guillaume Darrasse-Jèze, Gilles Marodon, Benoît L. Salomon, Martin Catala, and David Klatzmann From the Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Université Pierre et Marie Curie (UPMC)/Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 7087, Paris, France; Département de Génétique, Cytogénétique et Embryologie and UPMC/CNRS UMR 7000, Paris, France; and Service de Biothérapie, Hôpital Pitié-Salpêtrière, Paris, France. 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 mice and humans. 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. Together with the first mature T cells, thymic CD4+CD25+ cells were detected as early as 13 weeks of gestation. 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% to 7%, similar to the proportion observed in infant thymi. Extrathymic 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 cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) 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. (Blood. 2005;105:4715-4721) 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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