SEARCH:   Advanced

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 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 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 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. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Pathologic clonal cytotoxic T-cell responses: nonrandom 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 From the Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, and the Department of Clinical Pathology, Cleveland Clinic Foundation, Cleveland, OH; Institute of Medical Immunology, Charite Medical School, Berlin, Germany; Penn State Cancer Institute, Hershey, PA; and Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD. T-cell large granular lymphocyte (T-LGL) leukemia is a clonal lymphoproliferation of cytotoxic T cells (CTLs) 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 beta (VB)–chain complementarity-determining region 3 (CDR3), 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 4 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 2 patients with identical immunodominant CDR3 sequence. Moreover, we found similarity between multiple immunodominant clonotypes and codominant as well as a nonexpanded, "supporting" clonotypes. The data suggest a nonrandom clonal selection in T-LGL, possibly driven by a common antigen. In contrast, the physiologic 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: 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] J. Yang, P. K. Epling-Burnette, J. S. Painter, J. Zou, F. Bai, S. Wei, and T. P. Loughran Jr Antigen activation and impaired Fas-induced death-inducing signaling complex formation in T-large-granular lymphocyte leukemia Blood, February 1, 2008; 111(3): 1610 - 1616. [Abstract] [Full Text] [PDF] C. L. O'Keefe, L. Gondek, R. Davis, E. Kuczkowski, R. M. Sobecks, A. Rodriguez, Y. Narvaez, Z. McIver, R. Tuthill, M. Laughlin, et al. Molecular Analysis of Alloreactive CTL Post-Hemopoietic Stem Cell Transplantation J. Immunol., August 1, 2007; 179(3): 2013 - 2022. [Abstract] [Full Text] [PDF] S. Y. Kordasti, W. Ingram, J. Hayden, D. Darling, L. Barber, B. Afzali, G. Lombardi, M. W. Wlodarski, J. P. Maciejewski, F. Farzaneh, et al. CD4+CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS) Blood, August 1, 2007; 110(3): 847 - 850. [Abstract] [Full Text] [PDF] L. Gargiulo, S. Lastraioli, G. Cerruti, M. Serra, F. Loiacono, S. Zupo, L. Luzzatto, and R. Notaro Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria Blood, June 1, 2007; 109(11): 5036 - 5042. [Abstract] [Full Text] [PDF] P. Garrido, F. Ruiz-Cabello, P. Barcena, Y. Sandberg, J. Canton, M. Lima, A. Balanzategui, M. Gonzalez, M. A. Lopez-Nevot, A. W. Langerak, et al. Monoclonal TCR-V 13.1+/CD4+/NKa+/CD8 /+dim T-LGL lymphocytosis: evidence for an antigen-driven chronic T-cell stimulation origin Blood, June 1, 2007; 109(11): 4890 - 4898. [Abstract] [Full Text] [PDF] M. W. Wlodarski, L. P. Gondek, Z. P. Nearman, M. Plasilova, M. Kalaycio, E. D. Hsi, and J. P. Maciejewski Molecular strategies for detection and quantitation of clonal cytotoxic T-cell responses in aplastic anemia and myelodysplastic syndrome Blood, October 15, 2006; 108(8): 2632 - 2641. [Abstract] [Full Text] [PDF] H. Szpurka, R. Tiu, G. Murugesan, S. Aboudola, E. D. Hsi, K. S. Theil, M. A. Sekeres, and J. P. Maciejewski Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation Blood, October 1, 2006; 108(7): 2173 - 2181. [Abstract] [Full Text] [PDF] L. Sokol and T. P. Loughran Jr. Large granular lymphocyte leukemia. Oncologist, March 1, 2006; 11(3): 263 - 273. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020