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Blood, 1 November 2005, Vol. 106, No. 9, pp. 2936-2943. Prepublished online as a Blood First Edition Paper on June 30, 2005; DOI 10.1182/blood-2005-05-1826. This Article Full Text Full Text (PDF) Erratum (v112,p3530) All Versions of this Article: 2005-05-1826v1 106/9/2936    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 Tan, P. H. Articles by George, A. J. T. Search for Related Content PubMed PubMed Citation Articles by Tan, P. H. Articles by George, A. J. T. Related Collections Immunobiology Transplantation Plenary Papers Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPERS Creation of tolerogenic human dendritic cells via intracellular CTLA4: a novel strategy with potential in clinical immunosuppression Peng H. Tan, John B. Yates, Shao-An Xue, Cliburn Chan, William J. Jordan, Jennifer E. Harper, Martin P. Watson, Rong Dong, Mary A. Ritter, Robert I. Lechler, Giovanna Lombardi, and Andrew J. T. George From the Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom. Activation of T lymphocytes requires the recognition of peptide–major histocompatibility complexes (MHCs) and costimulatory signals provided by antigen-presenting cells (APCs). It has been shown that T-cell activation without costimulation can lead to anergy. In this study, we developed a novel strategy to inhibit expression of B7 molecules (CD80/86) by transfecting APCs with a gene construct encoding a modified cytotoxic T lymphocyte antigen 4 (CTLA4) molecule (CTLA4-KDEL) that is targeted to the endoplasmic reticulum (ER). APCs expressing this construct failed to express CD80/86 on their surface, were unable to stimulate allogeneic and peptide-specific T-cell responses, and induced antigen-specific anergy of the responding T cells. Cells expressing CTLA4-KDEL do not up-regulate the indoleamine 2, 3-dioxygenase enzyme, unlike cells treated with soluble CTLA4-immunoglobin (Ig). This gene-based strategy to knock out surface receptors is an attractive alternative to using immature dendritic cells for preventing transplant rejection and treating of autoimmune diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Costimulatory blockade: act II David H. Munn Blood 2005 106: 2926-2927. [Full Text] [PDF] This article has been cited by other articles: P. Hubert, N. Jacobs, J.-H. Caberg, J. Boniver, and P. Delvenne The cross-talk between dendritic and regulatory T cells: good or evil? J. Leukoc. Biol., October 1, 2007; 82(4): 781 - 794. [Abstract] [Full Text] [PDF] D.-Y. Hou, A. J. Muller, M. D. Sharma, J. DuHadaway, T. Banerjee, M. Johnson, A. L. Mellor, G. C. Prendergast, and D. H. Munn Inhibition of Indoleamine 2,3-Dioxygenase in Dendritic Cells by Stereoisomers of 1-Methyl-Tryptophan Correlates with Antitumor Responses Cancer Res., January 15, 2007; 67(2): 792 - 801. [Abstract] [Full Text] [PDF] S. Rutella, S. Danese, and G. Leone Tolerogenic dendritic cells: cytokine modulation comes of age Blood, September 1, 2006; 108(5): 1435 - 1440. [Abstract] [Full Text] [PDF]

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