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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2003-01-0182. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0182v1 102/3/1057    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 Mackus, W. J. M. Articles by van Oers, M. H. J. Search for Related Content PubMed PubMed Citation Articles by Mackus, W. J. M. Articles by van Oers, M. H. J. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2003, Vol. 102, No. 3, pp. 1057-1063 NEOPLASIA Expansion of CMV-specific CD8+CD45RA+CD27- T cells in B-cell chronic lymphocytic leukemia Wendelina J. M. Mackus, Florine N. J. Frakking, Annette Grummels, Laila E. Gamadia, Godelieve J. de Bree, Dörte Hamann, René A. W. van Lier, and Marinus H. J. van Oers From the Department of Hematology, Academic Medical Center, Laboratory for Experimental Immunology, Academic Medical Center, University of Amsterdam, The Netherlands In patients with B-cell chronic lymphocytic leukemia (B-CLL), the absolute number of T cells is increased. Although it has been suggested that these T cells might be tumor specific, concrete evidence for this hypothesis is lacking. We performed a detailed immunophenotypic analysis of the T-cell compartment in the peripheral blood of 28 patients with B-CLL (Rai 0, n = 12; Rai I-II, n = 10; Rai III-IV, n = 6) and 12 healthy age-matched controls and measured the ability of these patients to mount specific immune responses. In all Rai stages a significant increase in the absolute numbers of CD3+ cells was observed. Whereas the number of CD4+ cells was not different from controls, patients with B-CLL showed significantly increased relative and absolute numbers of CD8+ cells, which exhibited a CD45RA+CD27- cytotoxic phenotype. Analysis of specific immune responses with tetrameric cytomegalovirus (CMV)–peptide complexes showed that patients with B-CLL had significantly increased numbers of tetramer-binding CMV-specific CD8+ T cells. The rise in the total number of CD8+ cytotoxic T cells was evident only in CMV-seropositive B-CLL patients. Thus, our data suggest that in patients with B-CLL the composition of T cells is shifted toward a CD8+ cytotoxic cell type in an effort to control infections with persistent viruses such as CMV. Moreover, they offer an explanation for the high incidence of CMV reactivation in CLL patients treated with T cell–depleting agents, such as the monoclonal antibody (mAb) alemtuzumab (Campath; -CD52 mAb). Furthermore, because in CMV-seronegative patients no increase in cytotoxic CD8+ T cells is found, our studies do not support the hypothesis that tumor-specific T cells account for T-cell expansion in B-CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. O'Brien, F. Ravandi, T. Riehl, W. Wierda, X. Huang, J. Tarrand, B. O'Neal, H. Kantarjian, and M. Keating Valganciclovir prevents cytomegalovirus reactivation in patients receiving alemtuzumab-based therapy Blood, February 15, 2008; 111(4): 1816 - 1819. [Abstract] [Full Text] [PDF] A. P. Kater, M. H. J. van Oers, and T. J. Kipps Cellular immune therapy for chronic lymphocytic leukemia Blood, October 15, 2007; 110(8): 2811 - 2818. [Abstract] [Full Text] [PDF] K. N. Potter, C. I. Mockridge, L. Neville, I. Wheatley, M. Schenk, J. Orchard, A. S. Duncombe, G. Packham, and F. K. Stevenson Structural and Functional Features of the B-Cell Receptor in IgG-Positive Chronic Lymphocytic Leukemia. Clin. Cancer Res., March 15, 2006; 12(6): 1672 - 1679. [Abstract] [Full Text] [PDF] R. Mous, P. S. Savage, E. B. Remmerswaal, R. A.W. van Lier, E. Eldering, and M. H.J. Van Oers Redirection of CMV Specific CTL towards B-CLL Via CD20 Targeted HLA/CMV Complexes. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 449 - 449. [Abstract] E. M. M. van Leeuwen, G. J. de Bree, E. B. M. Remmerswaal, S.-L. Yong, K. Tesselaar, I. J. M. t. Berge, and R. A. 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