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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-08-2408. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-08-2408v1 101/8/3198    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 Bigouret, V. Articles by Roosnek, E. Search for Related Content PubMed PubMed Citation Articles by Bigouret, V. Articles by Roosnek, E. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2003, Vol. 101, No. 8, pp. 3198-3204 NEOPLASIA Monoclonal T-cell expansions in asymptomatic individuals and in patients with large granular leukemia consist of cytotoxic effector T cells expressing the activating CD94:NKG2C/E and NKD2D killer cell receptors Valérie Bigouret, Till Hoffmann, Lionel Arlettaz, Jean Villard, Marco Colonna, André Ticheli, Alois Gratwohl, Kaveh Samii, Bernard Chapuis, Nathalie Rufer, and Eddy Roosnek From the Division of Immunology and Allergology and the Division of Hematology, University Hospital, Geneva, Switzerland; the Institute for Transfusion Medicine, Heinrich Heine University, Duesseldorf, Germany; the Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO; Diagnostic and Therapeutic Hematology, Kantonsspital, Basel, Switzerland; and NCCR Molecular Oncology, Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland. We have analyzed the phenotype, cytokine profile, and mitotic history (telomere length) of monoclonal T-cell expansions in 5 CD3+ T-cell large granular lymphocyte (TLGL) leukemia patients by fluorescence activated cell sorting (FACS) and single-cell polymerase chain reaction (PCR). We confirm that the common phenotype of TLGL leukemia is CD3+CD8+CD45RA+CD27CD94+(CD57+). Interestingly, the C-type lectin-like type killer cell receptor CD94 was invariably associated with the activating form of its signal-transducing molecule NKG2. Furthermore, when judged by criteria such as interferon gamma (IFN-)/tumor necrosis factor (TNF) production, expression of granzyme, FasL, and NKG2D, the TLGL cells had all the features of a cytotoxic effector T cell. Telomere shortening in TLGL cells was in the normal range for CD8+ T cells, indicating that they had not divided significantly more than chronically stimulated CD8+ T cells in healthy individuals. In 25 of 27 controls, cells with a TLGL phenotype occurred at low (1%-3%) frequencies. However, in the other 2 individuals (ages 28-36 years), large stable (> 3 years) monoclonal expansions of CD3+CD8+CD45RA+CD27CD57+CD94+ NKG2C+ were found which rendered these controls phenotypically indistinguishable from TLGL leukemia patients. We believe that the TLGL clonopathy, rather than being of a neoplastic nature, is more likely an extreme manifestation of the large and stable clonal size characteristic of CD8+ effector cells. Such a TLGL clone consisting of cells without any particular pathologic trait might exist in a considerable number of individuals. Clinical symptoms may occur in individuals in whom the TLGL clone encounters antigen and is triggered to produce large amounts of effector molecules that dysregulate the immune system, which could manifest itself as autoimmunity or as a FasL-mediated neutropenia. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. W. Wlodarski, Z. Nearman, A. Jankowska, N. Babel, J. Powers, P. Leahy, H.-D. Volk, and J. P. Maciejewski Phenotypic differences between healthy effector CTL and leukemic LGL cells support the notion of antigen-triggered clonal transformation in T-LGL leukemia J. Leukoc. Biol., March 1, 2008; 83(3): 589 - 601. [Abstract] [Full Text] [PDF] C. Barbey, E. Pradervand, N. Barbier, and F. Spertini Ex Vivo Monitoring of Antigen-Specific CD4+ T Cells after Recall Immunization with Tetanus Toxoid Clin. 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