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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6465-6476. Prepublished online as a Blood First Edition Paper on April 15, 2009; DOI 10.1182/blood-2009-02-203307. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-02-203307v1 113/25/6465    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 CrossRef Google Scholar Articles by Zhou, W. Articles by Diamond, D. J. PubMed PubMed Citation Articles by Zhou, W. Articles by Diamond, D. J. Related Collections Immunobiology Transplantation Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients Wendi Zhou1,2,*, Jeff Longmate3,*, Simon F. Lacey1,2, Joycelynne M. Palmer3, Ghislaine Gallez-Hawkins2, Lia Thao2, Ricardo Spielberger4, Ryotaro Nakamura4, Stephen J. Forman4, John A. Zaia2, and Don J. Diamond1,2 1 Division of Translational Vaccine Research, 2 Department of Virology, and 3 Division of Biostatistics, Beckman Research Institute of the City of Hope, and 4 Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA Reconstitution of cytomegalovirus (CMV)–specific CD8+ T cells is essential to the control of CMV infection in CMV-positive recipients (R+) after allogeneic hematopoietic stem cell transplantation (HCT). Six-color flow cytometry was used to assess the functional profile of CMV-specific CD8+ T cells in 62 of 178 R+ HCT recipients followed virologically for CMV reactivation. R+ recipients receiving grafts from CMV-negative donors (D–; D–/R+) reconstituted fewer multifunctional CD8+ T cells expressing tumor necrosis factor- (TNF-), macrophage inflammatory protein-1β (MIP-1β), and CD107 in addition to interferon- (IFN-), compared with D+/R+ recipients. Unlike monofunctional CD8+ T cells secreting IFN-, which were abundantly generated during CMV reactivation in D–/R+ recipients, the relative lack of multifunctional CD8+ T cells persisted until at least 1 year post-HCT. D–/R+ recipients were more likely to require recurrent and prolonged use of antivirals. These findings were robust to statistical adjustment for pretransplant factors, as well as for posttransplant factors including graft-versus-host disease (GVHD) and its treatment by steroids. These analyses suggest that D+/R+ transplants, on average, generate higher levels of multifunctional CMV-specific T cells and require less antiviral therapy compared with D–/R+ HCT recipients. These results highlight the benefit of D+ donors in improving outcomes of R+ HCT recipients by reducing the duration and recurrent need of antiviral treatment, aided by increased levels of multifunctional CMV-specific T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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