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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1086-1094. Prepublished online as a Blood First Edition Paper on September 21, 2006; DOI 10.1182/blood-2006-03-011643. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-03-011643v1 109/3/1086    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 Chiu, C. Articles by Callan, M. F. Search for Related Content PubMed PubMed Citation Articles by Chiu, C. Articles by Callan, M. F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 22, 2006 Accepted September 12, 2006 Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo Christopher Chiu*, Adrian G Heaps, Vincenzo Cerundolo, Andrew J McMichael, Charles R Bangham, and Margaret FC Callan Department of Immunology, Wright-Fleming Institute, Imperial College, London, UK Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK Division of Medicine, Department of Rheumatology, Imperial College, London, UK * Corresponding author; email: c.chiu{at}imperial.ac.uk. Functional studies show that programming of CD8+ T-cells occurs early after initial antigen encounter within as little as 2 hours. To define the molecular basis of these events, we transferred TCR transgenic T-cells from F5 Rag-/- mice into naive recipients and stimulated them with recombinant Vaccinia expressing the immunodominant influenza epitope NP366-374. Transcription in epitope-specific CTLs was analysed using Affymetrix 430 2.0 GeneChips and quantitative PCR. We demonstrated an early transcriptional burst with the greatest number of genes reaching peak expression 12 hours post-stimulation. Using in vivo cytotoxicity assays we demonstrated that early up-regulation of cytolytic genes was accompanied by acquisition of killing capacity within 24 hours of stimulation. However, T-cell proliferation was not observed until 48 hours. We therefore conclude that clonal expansion rather than acquisition of effector function is the rate-limiting step in the development of a primary CTL response. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. E. Speiser, P. Baumgaertner, V. Voelter, E. Devevre, C. Barbey, N. Rufer, and P. Romero Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen PNAS, March 11, 2008; 105(10): 3849 - 3854. [Abstract] [Full Text] [PDF] Z. Xiao, M. F. Mescher, and S. C. Jameson Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation J. Exp. Med., October 29, 2007; 204(11): 2667 - 2677. [Abstract] [Full Text] [PDF] V. V. Ganusov, D. Milutinovic, and R. J. De Boer IL-2 Regulates Expansion of CD4+ T Cell Populations by Affecting Cell Death: Insights from Modeling CFSE Data J. Immunol., July 15, 2007; 179(2): 950 - 957. [Abstract] [Full Text] [PDF] M. R. Jenkins, K. Kedzierska, P. C. Doherty, and S. J. Turner Heterogeneity of Effector Phenotype for Acute Phase and Memory Influenza A Virus-Specific CTL J. Immunol., July 1, 2007; 179(1): 64 - 70. [Abstract] [Full Text] [PDF]

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