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Blood, 1 July 2006, Vol. 108, No. 1, pp. 11-18. Prepublished online as a Blood First Edition Paper on March 16, 2006; DOI 10.1182/blood-2006-01-0144. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2006-01-0144v1 108/1/11    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 Sauce, D. Articles by Rickinson, A. B. Search for Related Content PubMed PubMed Citation Articles by Sauce, D. Articles by Rickinson, A. B. Related Collections Immunobiology Plenary Papers Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPERS EBV-associated mononucleosis leads to long-term global deficit in T-cell responsiveness to IL-15 Delphine Sauce, Martin Larsen, S. John Curnow, Alison M. Leese, Paul A. H. Moss, Andrew D. Hislop, Michael Salmon, and Alan B. Rickinson From the Cancer Research United Kingdom (CRUK) Institute for Cancer Studies and the Medical Research Council (MRC) Centre for Immune Regulation, University of Birmingham, United Kingdom. In mice, interleukin-7 (IL-7) and IL-15 are involved in T-cell homeostasis and the maintenance of immunologic memory. Here, we follow virus-induced responses in infectious mononucleosis (IM) patients from primary Epstein-Barr virus (EBV) infection into long-term virus carriage, monitoring IL-7 and IL-15 receptor (IL-R) expression by antibody staining and cytokine responsiveness by STAT5 phosphorylation and in vitro proliferation. Expression of IL-7R was lost from all CD8+ T cells, including EBV epitope-specific populations, during acute IM. Thereafter, expression recovered quickly on total CD8+ cells but slowly and incompletely on EBV-specific memory cells. Expression of IL-15R was also lost in acute IM and remained undetectable thereafter not just on EBV-specific CD8+ populations but on the whole peripheral T- and natural killer (NK)-cell pool. This deficit, correlating with defective IL-15 responsiveness in vitro, was consistently observed in patients up to 14 years after IM but not in patients after cytomegalovirus (CMV)-associated mononucleosis, or in healthy EBV carriers with no history of IM, or in EBV-naive individuals. By permanently scarring the immune system, symptomatic primary EBV infection provides a unique cohort of patients through which to study the effects of impaired IL-15 signaling on human lymphocyte functions in vitro and in vivo. (Blood. 2006;108:11-18) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The kiss that scars M. Victor Lemas and Richard F. Ambinder Blood 2006 108: 8. [Full Text] [PDF] This article has been cited by other articles: D. Sauce, M. Larsen, R. J. M. Abbott, A. D. Hislop, A. M. Leese, N. Khan, L. Papagno, G. J. Freeman, and A. B. Rickinson Upregulation of Interleukin 7 Receptor Alpha and Programmed Death 1 Marks an Epitope-Specific CD8+ T-Cell Response That Disappears following Primary Epstein-Barr Virus Infection J. Virol., September 15, 2009; 83(18): 9068 - 9078. [Abstract] [Full Text] [PDF] J. Giron-Michel, F. Menard, S. Negrini, A. Devocelle, B. Azzarone, and C. Besson EBV-associated mononucleosis does not induce long-term global deficit in T-cell responsiveness to IL-15 Blood, May 7, 2009; 113(19): 4541 - 4547. [Abstract] [Full Text] [PDF] A. A. Chanan-Khan, A. Whitworth, N. Bangia, C. W. Porter, and K. Lee Lenalidomide-Associated Tumor Flare Reaction Is Manageable in Patients With Chronic Lymphocytic Leukemia J. Clin. Oncol., October 10, 2008; 26(29): 4851 - 4852. [Full Text] [PDF] S. L. Elliott, A. Suhrbier, J. J. Miles, G. Lawrence, S. J. Pye, T. T. Le, A. Rosenstengel, T. Nguyen, A. Allworth, S. R. Burrows, et al. Phase I Trial of a CD8+ T-Cell Peptide Epitope-Based Vaccine for Infectious Mononucleosis J. Virol., February 1, 2008; 82(3): 1448 - 1457. [Abstract] [Full Text] [PDF] V. Hadinoto, M. Shapiro, T. C. Greenough, J. L. Sullivan, K. Luzuriaga, and D. A. Thorley-Lawson On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis Blood, February 1, 2008; 111(3): 1420 - 1427. [Abstract] [Full Text] [PDF] G. D. Shah, J. Yahalom, D. D. Correa, R. K. Lai, J. J. Raizer, D. Schiff, R. LaRocca, B. Grant, L. M. DeAngelis, and L. E. Abrey Combined Immunochemotherapy With Reduced Whole-Brain Radiotherapy for Newly Diagnosed Primary CNS Lymphoma J. Clin. Oncol., October 20, 2007; 25(30): 4730 - 4735. [Abstract] [Full Text] [PDF] B. Ahmed, J. A. Tschen, P. R. Cohen, M. H. Zaki, P. L. Rady, S. K. Tyring, R. E. Corringham, and R. Kurzrock Cutaneous castleman's disease responds to anti interleukin-6 treatment Mol. Cancer Ther., September 1, 2007; 6(9): 2386 - 2390. [Abstract] [Full Text] [PDF] S. S. Cush, K. M. Anderson, D. H. Ravneberg, J. L. Weslow-Schmidt, and E. Flano Memory Generation and Maintenance of CD8+ T Cell Function during Viral Persistence J. Immunol., July 1, 2007; 179(1): 141 - 153. [Abstract] [Full Text] [PDF] T. R. Nielsen, K. Rostgaard, N. M. Nielsen, N. Koch-Henriksen, S. Haahr, P. S. Sorensen, and H. Hjalgrim Multiple Sclerosis After Infectious Mononucleosis Arch Neurol, January 1, 2007; 64(1): 72 - 75. [Abstract] [Full Text] [PDF]

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