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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3565-3572. Prepublished online as a Blood First Edition Paper on December 11, 2003; DOI 10.1182/blood-2003-09-3056. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-09-3056v1 103/9/3565    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 Rauser, G. Articles by Topp, M. S. Search for Related Content PubMed PubMed Citation Articles by Rauser, G. Articles by Topp, M. S. Related Collections Immunobiology Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants Georg Rauser, Hermann Einsele, Christian Sinzger, Dorothee Wernet, Gabriele Kuntz, Mario Assenmacher, John D. M. Campbell, and Max S. Topp From Medizinische Klinik II, Medizinische Virologie, and Transfusionsmedizin, Eberhard-Karls-Universität, Tübingen, Germany; and Miltenyi Biotec, Bergisch-Gladbach, Germany. Adoptive transfer of cytomegalovirus (CMV)-specific T cells can restore long-lasting, virus-specific immunity and clear CMV viremia in recipients of allogeneic stem cell transplants if CD4+ and CD8+ CMV-specific T cells are detected in the recipient after transfer. Current protocols for generating virus-specific T cells use live virus, require leukapheresis of the donor, and are time consuming. To circumvent these limitations, a clinical-scale protocol was developed to generate CMV-specific T cells by using autologous cellular and serum components derived from a single 500-mL blood draw. CMV-specific T cells were stimulated simultaneously with CMV-specific major histocompatibility complex class I (MHC I)- restricted peptides and CMV antigen. Activated T cells were isolated with the interferon- (IFN-) secretion assay and expanded for 10 days. In 8 randomly selected, CMV-seropositive donors, 1.34 x 108 combined CD4+ and CD8+ CMV-specific T cells, on average, were generated, as determined by antigen-triggered IFN- production. CMV-infected fibroblasts were efficiently lysed by the generated T cells, and CMV-specific CD4+ and CD8+ T cells expanded if they were stimulated with natural processed antigen. On the other hand, CD4+ and CD8+ T cell-mediated alloreactivity of generated CMV-specific T-cell lines was reduced compared with that of the starting population. In conclusion, the culture system developed allowed the rapid generation of allodepleted, highly enriched, combined CD4+ and CD8+ CMV-specific T cells under conditions mimicking good manufacturing practice. (Blood. 2004; 103:3565-3572) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Besold, N. Frankenberg, S. Pepperl-Klindworth, J. Kuball, M. Theobald, G. Hahn, and B. Plachter Processing and MHC class I presentation of human cytomegalovirus pp65-derived peptides persist despite gpUS2-11-mediated immune evasion J. Gen. Virol., May 1, 2007; 88(5): 1429 - 1439. [Abstract] [Full Text] [PDF] E. Adamopoulou, J. Diekmann, E. Tolosa, G. Kuntz, H. Einsele, H.-G. Rammensee, and M. S. Topp Human CD4+ T Cells Displaying Viral Epitopes Elicit a Functional Virus-Specific Memory CD8+ T Cell Response J. Immunol., May 1, 2007; 178(9): 5465 - 5472. [Abstract] [Full Text] [PDF] I. Jedema, P. Meij, E. Steeneveld, M. Hoogendoorn, B. A. Nijmeijer, M. van de Meent, S. A.P. van Luxemburg-Heijs, R. Willemze, and J.H. F. Falkenburg Early Detection and Rapid Isolation of Leukemia-Reactive Donor T Cells for Adoptive Transfer Using the IFN-{gamma} Secretion Assay Clin. Cancer Res., January 15, 2007; 13(2): 636 - 643. [Abstract] [Full Text] [PDF] D. Lilleri, G. Gerna, C. Fornara, L. Lozza, R. Maccario, and F. Locatelli Prospective simultaneous quantification of human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in young recipients of allogeneic hematopoietic stem cell transplants Blood, August 15, 2006; 108(4): 1406 - 1412. [Abstract] [Full Text] [PDF] O. Beck, M. S. Topp, U. Koehl, E. Roilides, M. Simitsopoulou, M. Hanisch, J. Sarfati, J. P. Latge, T. Klingebiel, H. Einsele, et al. Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus Blood, March 15, 2006; 107(6): 2562 - 2569. [Abstract] [Full Text] [PDF] F. Aversa, A. Terenzi, A. Tabilio, F. Falzetti, A. Carotti, S. Ballanti, R. Felicini, F. Falcinelli, A. Velardi, L. Ruggeri, et al. Full Haplotype-Mismatched Hematopoietic Stem-Cell Transplantation: A Phase II Study in Patients With Acute Leukemia at High Risk of Relapse J. Clin. Oncol., May 20, 2005; 23(15): 3447 - 3454. [Abstract] [Full Text] [PDF]

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