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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2399-2408. Prepublished online as a Blood First Edition Paper on June 14, 2005; DOI 10.1182/blood-2004-11-4315. This Article Full Text (PDF) All Versions of this Article: 2004-11-4315v1 106/7/2399    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 Poggi, A. Articles by Notaro, R. Search for Related Content PubMed PubMed Citation Articles by Poggi, A. Articles by Notaro, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 12, 2004 Accepted May 30, 2005 Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of peripheral blood T cells expressing activating isoforms of inhibiting superfamily receptors Alessandro Poggi*, Simone Negrini, Maria R Zocchi, Anna-Maria Massaro, Lucia Garbarino, Sonia Lastraioli, Lucia Gargiulo, Lucio Luzzatto, and Rosario Notaro Laboratory of Immunology, National Institute for Cancer Research, Genoa, Italy Laboratory of Immunology, National Institute for Cancer Research, Genoa, Italy; Laboratory of Clinical Immunology, Department of Internal Medicine, University of Genoa, Genoa, Italy Laboratory of Tumor Immunology, San Raffaele Scientific Institute, Milan, Italy Laboratory of Immunology, National Institute for Cancer Research, Genoa, Italy; Laboratory of Tumor Immunology, San Raffaele Scientific Institute, Milan, Italy Laboratory of Hystocompatibility /IBMDR, Galliera Hospital, Genoa, Italy Laboratory of Human Genetics, National Institute for Cancer Research, Genoa, Italy University of Genoa, Genoa, Italy * Corresponding author; email: alessandro.poggi{at}istge.it. Patients with paroxysmal nocturnal hemoglobinuria (PNH) have a large clonal population of blood cells deriving from hematopoietic stem cells (HSC) deficient in glycosylphosphatidylinositol (GPI)-anchored surface molecules. A current model postulates that PNH arises through negative selection against normal HSCs exerted by autoreactive T cells, whereas PNH HSCs escape damage. We have investigated the Inhibitory Receptor Superfamily (IRS) system in 13 PNH patients. We found a slight increase in the proportion of T cells expressing IRS. In contrast to what applies to healthy donors, the engagement of IRS molecules on T cells from PNH patients elicited a powerful cytolytic activity in a re-directed killing assay, indicating that these IRS belong to the activating type. This was confirmed by clonal analysis: activating IRS+ T cell clones are >50% in PNH patients but < 5% in healthy donors. Moreover, the ligation of IRS induces (a) production of TNF and IFN and (b) brisk cytolytic activity against cells bearing appropriate IRS counter-ligands. In addition, these IRS+ T cells show NK-like cytolytic activity to which GPI- cells were less sensitive than GPI+ cells. Thus, T cells with NK-like features, expressing the activating isoforms of IRS, may include effector cells involved in the pathogenesis of PNH. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Dingli, L. Luzzatto, and J. M. Pacheco Neutral evolution in paroxysmal nocturnal hemoglobinuria PNAS, November 25, 2008; 105(47): 18496 - 18500. [Abstract] [Full Text] [PDF] S. Patterson, A. Chaidos, D. C. A. Neville, A. Poggi, T. D. Butters, I. A. G. Roberts, and A. Karadimitris Human Invariant NKT Cells Display Alloreactivity Instructed by Invariant TCR-CD1d Interaction and Killer Ig Receptors J. Immunol., September 1, 2008; 181(5): 3268 - 3276. [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] J. Chen, F. M. Ellison, M. A. Eckhaus, A. L. Smith, K. Keyvanfar, R. T. Calado, and N. S. Young Minor Antigen H60-Mediated Aplastic Anemia Is Ameliorated by Immunosuppression and the Infusion of Regulatory T Cells J. Immunol., April 1, 2007; 178(7): 4159 - 4168. [Abstract] [Full Text] [PDF] N. S. Young, R. T. Calado, and P. Scheinberg Current concepts in the pathophysiology and treatment of aplastic anemia Blood, October 15, 2006; 108(8): 2509 - 2519. [Abstract] [Full Text] [PDF] N. S. Young Pathophysiologic Mechanisms in Acquired Aplastic Anemia Hematology, January 1, 2006; 2006(1): 72 - 77. [Abstract] [Full Text] [PDF]

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