SEARCH:   Advanced

Blood, 1 April 2005, Vol. 105, No. 7, pp. 2828-2835. Prepublished online as a Blood First Edition Paper on November 30, 2004; DOI 10.1182/blood-2004-07-2583. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2583v1 105/7/2828    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 Fischer, K. Articles by Mackensen, A. Search for Related Content PubMed PubMed Citation Articles by Fischer, K. Articles by Mackensen, A. Related Collections Transplantation Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Isolation and characterization of human antigen-specific TCR+ CD4-CD8- double-negative regulatory T cells Karin Fischer, Simon Voelkl, Jana Heymann, Grzegorz K. Przybylski, Krishna Mondal, Monika Laumer, Leoni Kunz-Schughart, Christian A. Schmidt, Reinhard Andreesen, and Andreas Mackensen From the Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany; Department of Hematology and Oncology, University Medical Center, Ernst-Moritz-Arndt-University, Greifswald, Germany; Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland; and Institute of Pathology, University of Regensburg, Regensburg, Germany. Down-regulation of immune responses by regulatory T (Treg) cells is an important mechanism involved in the induction of tolerance to allo-antigens (Ags). Recently, a novel subset of Ag-specific T-cell receptor (TCR)+ CD4-CD8- (double-negative [DN]) Treg cells has been found to be able to prevent the rejection of skin and heart allografts by specifically inhibiting the function of antigraft-specific CD8+ T cells. Here we demonstrate that peripheral DN Treg cells are present in humans, where they constitute about 1% of total CD3+ T cells, and consist of both naïve and Ag-experienced cells. Similar to murine DN Treg cells, human DN Treg cells are able to acquire peptide–HLA-A2 complexes from antigen-presenting cells by cell contact-dependent mechanisms. Furthermore, such acquired peptide-HLA complexes appear to be functionally active, in that CD8+ T cells specific for the HLA-A2–restricted self-peptide, Melan-A, became sensitive to apoptosis by neighboring DN T cells after acquisition of Melan-A–HLA-A2 complexes and revealed a reduced proliferative response. These results demonstrate for the first time that a sizable population of peripheral DN Treg cells, which are able to suppress Ag-specific T cells, exists in humans. DN Treg cells may serve to limit clonal expansion of allo-Ag–specific T cells after transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Bristeau-Leprince, V. Mateo, A. Lim, A. Magerus-Chatinet, E. Solary, A. Fischer, F. Rieux-Laucat, and M.-L. Gougeon Human TCR {alpha}/{beta}+ CD4-CD8- Double-Negative T Cells in Patients with Autoimmune Lymphoproliferative Syndrome Express Restricted V{beta} TCR Diversity and Are Clonally Related to CD8+ T Cells J. Immunol., July 1, 2008; 181(1): 440 - 448. [Abstract] [Full Text] [PDF] H. Tuovinen, E. Kekalainen, L. H. Rossi, J. Puntila, and T. Petteri Arstila Cutting Edge: Human CD4-CD8- Thymocytes Express FOXP3 in the Absence of a TCR J. Immunol., March 15, 2008; 180(6): 3651 - 3654. [Abstract] [Full Text] [PDF] D. T. Teachey, A. E. Seif, V. I. Brown, M. Bruno, R. M. Bunte, Y. J. Chang, J. K. Choi, J. D. Fish, J. Hall, G. S. Reid, et al. Targeting Notch signaling in autoimmune and lymphoproliferative disease Blood, January 15, 2008; 111(2): 705 - 714. [Abstract] [Full Text] [PDF] W. Chen, J. Diao, S. M. Stepkowski, and L. Zhang Both Infiltrating Regulatory T Cells and Insufficient Antigen Presentation Are Involved in Long-Term Cardiac Xenograft Survival J. Immunol., August 1, 2007; 179(3): 1542 - 1548. [Abstract] [Full Text] [PDF] U. Feger, E. Tolosa, Y.-H. Huang, A. Waschbisch, T. Biedermann, A. Melms, and H. Wiendl HLA-G expression defines a novel regulatory T-cell subset present in human peripheral blood and sites of inflammation Blood, July 15, 2007; 110(2): 568 - 577. [Abstract] [Full Text] [PDF] Z.-X. Zhang, Y. Ma, H. Wang, J. Arp, J. Jiang, X. Huang, K. M. He, B. Garcia, J. Madrenas, and R. Zhong Double-Negative T Cells, Activated by Xenoantigen, Lyse Autologous B and T Cells Using a Perforin/Granzyme-Dependent, Fas-Fas Ligand-Independent Pathway J. Immunol., November 15, 2006; 177(10): 6920 - 6929. [Abstract] [Full Text] [PDF] D. T. Teachey, D. A. Obzut, K. Axsom, J. K. Choi, K. C. Goldsmith, J. Hall, J. Hulitt, C. S. Manno, J. M. Maris, N. Rhodin, et al. Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS) Blood, September 15, 2006; 108(6): 1965 - 1971. [Abstract] [Full Text] [PDF] M. S. Ford, Z.-X. Zhang, W. Chen, and L. Zhang Double-Negative T Regulatory Cells Can Develop Outside the Thymus and Do Not Mature from CD8+ T Cell Precursors. J. Immunol., September 1, 2006; 177(5): 2803 - 2809. [Abstract] [Full Text] [PDF] C. W. Thomson, W. A. Teft, W. Chen, B. P.-L. Lee, J. Madrenas, and L. Zhang FcR{gamma} Presence in TCR Complex of Double-Negative T Cells Is Critical for Their Regulatory Function J. Immunol., August 15, 2006; 177(4): 2250 - 2257. [Abstract] [Full Text] [PDF] L. Rinaldi, P. Gallo, M. Calabrese, F. Ranzato, D. Luise, D. Colavito, M. Motta, A. Guglielmo, E. Del Giudice, C. Romualdi, et al. Longitudinal analysis of immune cell phenotypes in early stage multiple sclerosis: distinctive patterns characterize MRI-active patients. Brain, August 1, 2006; 129(Pt 8): 1993 - 2007. [Abstract] [Full Text] [PDF] B. P.-L. Lee, W. Chen, H. Shi, S. D. Der, R. Forster, and L. Zhang CXCR5/CXCL13 Interaction Is Important for Double-Negative Regulatory T Cell Homing to Cardiac Allografts J. Immunol., May 1, 2006; 176(9): 5276 - 5283. [Abstract] [Full Text] [PDF] W. Chen, D. Zhou, J. R. Torrealba, T. K. Waddell, D. Grant, and L. Zhang Donor Lymphocyte Infusion Induces Long-Term Donor-Specific Cardiac Xenograft Survival through Activation of Recipient Double-Negative Regulatory T Cells J. Immunol., September 1, 2005; 175(5): 3409 - 3416. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020