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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3371-3378. Prepublished online as a Blood First Edition Paper on July 25, 2006; DOI 10.1182/blood-2006-02-005660. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2006-02-005660v1 108/10/3371    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 Fritzsching, B. Articles by Suri-Payer, E. Search for Related Content PubMed PubMed Citation Articles by Fritzsching, B. Articles by Suri-Payer, E. Related Collections Apoptosis Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Naive regulatory T cells: a novel subpopulation defined by resistance toward CD95L-mediated cell death Benedikt Fritzsching, Nina Oberle, Eva Pauly, Robert Geffers, Jan Buer, Johannes Poschl, Peter Krammer, Otwin Linderkamp, and Elisabeth Suri-Payer From the Department of Neonatology, Children's Hospital, University of Heidelberg, Germany; Division of Immunogenetics, German Cancer Research Center, Heidelberg, Germany; Section of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Germany; and Department of Mucosal Immunity, German Research Center for Biotechnology, Braunschweig, Germany. Most CD4+CD25hiFOXP3+ regulatory T cells (Tregs) from adult peripheral blood express high levels of CD45RO and CD95 and are prone to CD95L-mediated apoptosis in contrast to conventional T cells (Tconvs). However, a Treg subpopulation remained consistently apoptosis resistant. Gene microarray and 6-color flow cytometry analysis including FOXP3 revealed an increase in naive T-cell markers on the CD95L-resistant Tregs compared with most Tregs. In contrast to Tregs found in adult humans, most CD4+CD25+FOXP3+ T cells found in cord blood are naive and exhibit low CD95 expression. Furthermore, most of these newborn Tregs are not sensitive toward CD95L similar to naive Tregs from adult individuals. After short stimulation with anti-CD3/CD28 monoclonal antibodies (mAbs), cord blood Tregs strongly up-regulated CD95 and were sensitized toward CD95L. This functional change was paralleled by a rapid up-regulation of memory T-cell markers on cord blood Tregs that are frequently found on adult memory Tregs. In summary, we show a clear functional difference between naive and memory Tregs that could result in different survival rates of those 2 cell populations in vivo. This new observation could be crucial for the planning of therapeutic application of Tregs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Venken, N. Hellings, T. Broekmans, K. Hensen, J.-L. Rummens, and P. Stinissen Natural Naive CD4+CD25+CD127low Regulatory T Cell (Treg) Development and Function Are Disturbed in Multiple Sclerosis Patients: Recovery of Memory Treg Homeostasis during Disease Progression J. Immunol., May 1, 2008; 180(9): 6411 - 6420. [Abstract] [Full Text] [PDF] B. Santner-Nanan, N. Seddiki, E. Zhu, V. Quent, A. Kelleher, B. F. de St Groth, and R. Nanan Accelerated age-dependent transition of human regulatory T cells to effector memory phenotype Int. Immunol., March 1, 2008; 20(3): 375 - 383. [Abstract] [Full Text] [PDF] A. K. Antons, R. Wang, K. Oswald-Richter, M. Tseng, C. W. Arendt, S. A. Kalams, and D. Unutmaz Naive Precursors of Human Regulatory T Cells Require FoxP3 for Suppression and Are Susceptible to HIV Infection J. Immunol., January 15, 2008; 180(2): 764 - 773. [Abstract] [Full Text] [PDF] W. Hansen, A. M. Westendorf, S. Reinwald, D. Bruder, S. Deppenmeier, L. Groebe, M. Probst-Kepper, A. D. Gruber, R. Geffers, and J. Buer Chronic Antigen Stimulation In Vivo Induces a Distinct Population of Antigen-Specific Foxp3 CD25 Regulatory T Cells J. Immunol., December 15, 2007; 179(12): 8059 - 8068. [Abstract] [Full Text] [PDF] D. Nummer, E. Suri-Payer, H. Schmitz-Winnenthal, A. Bonertz, L. Galindo, D. Antolovich, M. Koch, M. Buchler, J. Weitz, V. Schirrmacher, et al. Role of Tumor Endothelium in CD4+CD25+ Regulatory T Cell Infiltration of Human Pancreatic Carcinoma J Natl Cancer Inst, August 1, 2007; 99(15): 1188 - 1199. [Abstract] [Full Text] [PDF] J. Haas, B. Fritzsching, P. Trubswetter, M. Korporal, L. Milkova, B. Fritz, D. Vobis, P. H. Krammer, E. Suri-Payer, and B. Wildemann Prevalence of Newly Generated Naive Regulatory T Cells (Treg) Is Critical for Treg Suppressive Function and Determines Treg Dysfunction in Multiple Sclerosis J. Immunol., July 15, 2007; 179(2): 1322 - 1330. [Abstract] [Full Text] [PDF]

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