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Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2002-12-3689. This Article Full Text (PDF) All Versions of this Article: 2002-12-3689v1 102/9/3427    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 Gandhi, M. K Articles by Carmichael, A. J Search for Related Content PubMed PubMed Citation Articles by Gandhi, M. K Articles by Carmichael, A. J Social Bookmarking                   What's this? Submitted December 9, 2002 Accepted May 23, 2003 Late diversification in the clonal composition of Human Cytomegalovirus-specific CD8+ T-cells following allogeneic haemopoietic stem cell transplantation Maher K Gandhi, Mark R Wills, Georgina Okecha, Elizabeth K Day, Ray Hicks, Robert E Marcus, J G Sissons, and Andrew J Carmichael* Department of Hematology, University of Cambridge, Cambridge, United Kingdom Department of Medicine, University of Cambridge, Cambridge, United Kingdom * Corresponding author; email: ac71{at}medschl.cam.ac.uk. To investigate the mechanisms of human T-cell reconstitution following allogeneic haemopoietic stem cell transplantation (alloSCT), we analysed the clonal composition of human cytomegalovirus (HCMV)-specific or EBV-specific CD8+ T-cells in 10 alloSCT recipients and their donors. All virus-specific CD8+ T-cell clones isolated from recipients after alloSCT contained DNA of donor origin. In all six D+/R+ sibling alloSCTs from seropositive donors into seropositive recipients, donor virus-specific clones transferred in the allograft underwent early expansion and were maintained long-term in the recipient. In contrast, in two of three HCMV D+/R- alloSCT recipients in whom there was no detectable HCMV infection, donor HCMV-specific clones were undetectable whereas donor EBV-specific clones were maintained in the same EBV seropositive recipients, suggesting that transferred clones require antigen for their maintenance. Following D-/R+ transplantation from three seronegative donors into seropositive recipients, a delayed primary virus-specific CD8+ T-cell response was observed; in which the T-cells contained donor DNA suggesting that new antigen-specific T-cells arose in the recipient from donor-derived progenitors. In two of four HCMV D+/R+ sibling allograft recipients the clonal composition underwent diversification as compared to their donors, with delayed persistent expansion of HCMV-specific clones that were undetectable in the donor or in the recipient during the early months after transplantation; this diversification may represent expansion of new clones generated from donor-derived progenitors. We conclude that following alloSCT late diversification of the HCMV-specific CD8+ T-cell clonal repertoire can occur in response to persistent viral antigen. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Schub, I. G. Schuster, W. Hammerschmidt, and A. Moosmann CMV-Specific TCR-Transgenic T Cells for Immunotherapy J. Immunol., November 15, 2009; 183(10): 6819 - 6830. [Abstract] [Full Text] [PDF] S. Singh, P. van Hauten, K. Jones, K. Grimmett, A. K. Mills, and M. K. 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