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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 (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 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. Social Bookmarking                   What's this? Submitted August 8, 2002 Accepted December 3, 2002 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 Valerie Bigouret, Till Hoffmann, Lionel Arlettaz, Jean Villard, Marco Colonna, Andre Ticheli, Alois Gratwohl, Kaveh Samii, Bernard Chapuis, Nathalie Rufer, and Eddy Roosnek* Internal Medicine, University Hospital, Geneva, Geneva, Switzerland Institute for Transfusion Medicine, Heinrich Heine University, Duesseldorf, Germany Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA Diagnostic and Therapeutic Hematology, University Hospital, Basel, Basel, Switzerland NCCR Molecular Oncology, Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland * Corresponding author; email: roosnek{at}medecine.unige.ch. We have analyzed the phenotype, cytokine profile and the mitotic history (telomere length) of monoclonal T cell expansions in 5 CD3+ LGL-leukemia (TLGL) patients by FACS and single cell PCR. We confirm that the common phenotype of TLGL is CD3+CD8+CD45RA+CD27-CD94+(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 IFN-/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 normal individuals. In 25 of 27 controls, cells with a TLGL phenotype occurred at low (1-3%) frequencies. However, in the other 2 individuals (age 28-36) large stable (>3 years) monoclonal expansions of CD3+CD8+CD45RA+CD27-CD57+CD94+NKG2C+ were found which rendered these controls phenotypically indistinguishable from TLGL-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 pathological 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. 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. 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