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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-05-1387. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-05-1387v1 100/10/3690    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 Özdemir, E. Articles by Komanduri, K. V. Search for Related Content PubMed PubMed Citation Articles by Özdemir, E. Articles by Komanduri, K. V. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 November 2002, Vol. 100, No. 10, pp. 3690-3697 IMMUNOBIOLOGY Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells Evren Özdemir, Lisa S. St. John, Geraldine Gillespie, Sarah Rowland-Jones, Richard E. Champlin, Jeffrey J. Molldrem, and Krishna V. Komanduri From the Transplant Immunology Section, Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX; and MRC Human Immunology Unit, Institute of Molecular Medicine, Oxford, United Kingdom. Cytomegalovirus (CMV) infection causes significant morbidity and mortality in the setting of immunodeficiency, including the immune reconstitution phase following allogeneic stem cell transplantation (SCT). We assessed CMV-specific CD4+ and CD8+ T-cell responses in 87 HLA-A*0201-positive (A2+) and/or B*0702-positive (B7+) allogeneic stem cell transplant recipients using HLA-peptide tetramer staining and cytokine flow cytometry (CFC) to examine the association of CMV-specific immune reconstitution and CMV antigenemia following SCT. Strong CMV-specific T-cell responses recovered in most subjects (77 of 87, 88%) after SCT. Frequencies of CMV-specific CD8+ T cells were significantly higher in those subjects who experienced early antigenemia relative to those who did not (2.2% vs 0.33%, P = .0002), as were frequencies of CMV-specific CD4+ T cells (1.71% vs 0.75%, P = .002). Frequencies of CMV-specific CD8+ T cells were also higher in subjects experiencing late antigenemia (2.4% vs 0.57%). When we combined tetramer staining and an assessment of cytokine production in a single assay, we found that individuals who experienced CMV antigenemia had lower tumor necrosis factor- (TNF-)-producing fractions of tetramer-staining CMV-specific CD8+ T cells than subjects who did not (25% vs 65%, P = .015). Furthermore, individuals at high risk for CMV reactivation, including patients with acute graft-versus-host disease and those receiving steroids, had low fractions of cytokine-producing CMV-specific CD8+ T cells (25% and 27%, respectively). These data suggest that the inability to control CMV reactivation following allogeneic SCT is due to the impaired function of antigen-specific CD8+ T cells rather than an inability to recover sufficient numbers of CMV-specific T cells. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. M. Kelly, S. L. Highfill, A. 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