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Blood, 1 November 2006, Vol. 108, No. 9, pp. 3121-3127. Prepublished online as a Blood First Edition Paper on July 13, 2006; DOI 10.1182/blood-2006-03-006809. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-006809v1 108/9/3121    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 van Leeuwen, E. M. M. Articles by van Lier, R. A. W. Search for Related Content PubMed PubMed Citation Articles by van Leeuwen, E. M. M. Articles by van Lier, R. A. W. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Strong selection of virus-specific cytotoxic CD4+ T-cell clones during primary human cytomegalovirus infection Ester M. M. van Leeuwen, Ester B. M. Remmerswaal, Mirjam H. M. Heemskerk, Ineke J. M. ten Berge, and Rene A. W. van Lier From the Department of Experimental Immunology, and the Department of Internal Medicine, Division of Nephrology, Academic Medical Center, Amsterdam, the Netherlands; and the Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands To obtain insight into human CD4+ T cell differentiation and selection in vivo, we longitudinally studied cytomegalovirus (CMV)–specific CD4+ T cells after primary infection. Early in infection, CMV-specific CD4+ T cells have the appearance of interferon (IFN)–producing T-helper 1 (TH1) type cells, whereas during latency a large population of CMV-specific CD4+CD28– T cells emerges with immediate cytotoxic capacity. We demonstrate that CD4+CD28– T cells could lyse CMV antigen–expressing target cells in a class II–dependent manner. To clarify the clonal relationship between early and late CMV-specific CD4+ T cells, we determined their V usage and CDR3 sequences. The T-cell receptor (TCR) diversity in the early CMV-specific CD4+ T-cell population was high in contrast to the use of a very restricted set of TCR sequences in latent infection. T-cell clones found in the late CMV-specific CD4+ T-cell population could not be retrieved from the early CD4+ T-cell population, or were present only at a low frequency. The observation that dominant CMV-specific CD4+ clones during latency were only poorly represented in the acute phase suggests that after the initial control of the virus strong selection and/or priming of novel clones takes place in persistent infections in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. K. L. Cheung, D. J. Gottlieb, B. Plachter, S. Pepperl-Klindworth, S. Avdic, A. L. Cunningham, A. Abendroth, and B. Slobedman The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency Blood, November 5, 2009; 114(19): 4128 - 4137. [Abstract] [Full Text] [PDF] J. B. Sacha, J. P. Giraldo-Vela, M. B. Buechler, M. A. Martins, N. J. Maness, C. Chung, L. T. Wallace, E. J. Leon, T. C. Friedrich, N. A. Wilson, et al. 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