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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2769-2780. Prepublished online as a Blood First Edition Paper on May 24, 2005; DOI 10.1182/blood-2004-10-4045. This Article Full Text (PDF) All Versions of this Article: 2004-10-4045v1 106/8/2769    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 Wlodarski, M. W Articles by Maciejewski, J. P Search for Related Content PubMed PubMed Citation Articles by Wlodarski, M. W Articles by Maciejewski, J. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 20, 2004 Accepted April 12, 2005 Pathologic clonal cytotoxic T cell responses - non random nature of the T cell receptor restriction in large granular lymphocyte leukemia Marcin W Wlodarski, Christine O'Keefe, Evan C Howe, Antonio M Risitano, Alexander Rodriguez, Ilka Warshawsky, Thomas P Loughran, Jr., and Jaroslaw P Maciejewski* Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH, USA; Institute of Medical Immunology, Charite Medical School, Berlin, Germany Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH, USA Division of Hematology, Federico II University School of Medicine, Naples, Italy Department of Clinical Pathology, Cleveland Clinic Foundation, Cleveland, OH, USA Penn State Cancer Institute, Hershey, PA, USA * Corresponding author; email: maciejj{at}cc.ccf.org. Large granular lymphocyte leukemia (T-LGL) is a clonal lymphoproliferation of cytotoxic T cells (CTL) associated with cytopenias. T-LGL proliferation seems to be triggered/sustained by antigenic drive; it is likely that hematopoietic progenitors are the targets in this process. The antigen-specific portion of the T-cell receptor (TCR), the variable B-chain CDR3 region, can serve as a molecular signature (clonotype) of a T cell clone. We hypothesized that clonal CTL proliferation develops not randomly but in the context of an autoimmune response. We identified the clonotypic sequence of T-LGL clones in 60 patients, including 56 with known T-LGL and four with unspecified neutropenia. Our method also allowed for the measurement of clonal frequencies; a decrease in or loss of the pathogenic clonotype and restoration of the TCR repertoire was found after hematologic remission. We identified two patients with identical immunodominant CDR3 sequence. Moreover, we found similarity between multiple immunodominant clonotypes and codominant as well as a non-expanded, supporting clonotypes. The data suggest a non-random clonal selection in T-LGL possibly driven by a common antigen. In contrast, the physiological clonal CTL repertoire is highly diverse and we were not able to detect any significant clonal sharing in 26 healthy controls. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Zambello and G. Semenzato Large granular lymphocyte disorders: new etiopathogenetic clues as a rationale for innovative therapeutic approaches Haematologica, October 1, 2009; 94(10): 1341 - 1345. [Full Text] [PDF] S. R. Mohan, M. J. Clemente, M. Afable, H. N. Cazzolli, N. Bejanyan, M. W. Wlodarski, A. E. Lichtin, and J. P. 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[Abstract] [Full Text] [PDF]

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