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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 (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 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 Ozdemir, E. Articles by Komanduri, K. V Search for Related Content PubMed PubMed Citation Articles by Ozdemir, E. Articles by Komanduri, K. V Social Bookmarking                   What's this? Submitted May 13, 2002 Accepted June 29, 2002 Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells Evren Ozdemir, Lisa S St. John, Geraldine M Gillespie, Sarah L Rowland-Jones, Richard E Champlin, Jeffrey J Molldrem, and Krishna V Komanduri* Transplant Immunology Section, Dept. of Blood and Marrow Transplantation, M.D. Anderson Cancer Center, Houston, TX, USA MRC Human Immunology Unit, Institute of Molecular Medicine, Oxford, United Kingdom * Corresponding author; email: kkomandu{at}mail.mdanderson.org. 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=0.0002), as were frequencies of CMV-specific CD4+ T cells (1.71% vs. 0.75%, p=0.002). 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 TNF-producing fractions of tetramer-staining CMV-specific CD8+ T cells than subjects who did not (25% vs. 65%, p=0.015). 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. K. Kim, L. S. St. John, E. D. Wieder, J. Khalili, Q. Ma, and K. V. 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