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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 9, 2004 Accepted November 23, 2004 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* Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany Department of Hematology and Oncology, Ernst-Moritz-Arndt-University, Greifswald, Germany; Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland Department of Pathology, University of Regensburg, Regensburg, Germany Department of Hematology and Oncology, Ernst-Moritz-Arndt-University, Greifswald, Germany * Corresponding author; email: andreas.mackensen{at}klinik.uni-regensburg.de. Down-regulation of immune responses by regulatory T (Treg) cells is an important mechanism involved in the induction of tolerance to allo-antigens (Ag). 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 anti-graft-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 naive 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 sizeable population of peripheral DN Treg cells exists in humans that are able to suppress Ag-specific T cells. 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: J. C. Crispin and G. C. Tsokos Human TCR-{alpha}{beta}+ CD4- CD8- T Cells Can Derive from CD8+ T Cells and Display an Inflammatory Effector Phenotype J. Immunol., October 1, 2009; 183(7): 4675 - 4681. [Abstract] [Full Text] [PDF] M. S. Ford McIntyre, K. J. Young, J. Gao, B. Joe, and L. 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