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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 (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 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 Articles by van Lier, R. A Search for Related Content PubMed PubMed Citation Articles by van Leeuwen, E. M Articles by van Lier, R. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 2, 2006 Accepted June 26, 2006 Strong selection of virus-specific cytotoxic CD4+ T cell clones during primary human cytomegalovirus infection Ester M van Leeuwen*, Ester B Remmerswaal, Mirjam H Heemskerk, Ineke J ten Berge, and Rene A van Lier Department of Experimental Immunology, Dept. of Internal Medicine,Academic Medical Center, Amsterdam Dept. of Hematology, Leiden University Medical Center, Leiden, The Netherlands Department of Internal Medicine, Division of Nephrology, Academic Medical Center, Amsterdam Department of Experimental Immunology, Academic Medical Center, Amsterdam * Corresponding author; email: e.m.vanleeuwen{at}amc.uva.nl. To obtain insight in 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 IFN-producing TH1 type cells, whereas during latency a large population of CMV-specific CD4+CD28- T cells emerges with immediate cytotoxic capacity. We here 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 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, or only at low frequency, be retrieved from the early CD4+ T cell population. 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 man. 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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