1. Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients.
- Author
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Zhou W, Longmate J, Lacey SF, Palmer JM, Gallez-Hawkins G, Thao L, Spielberger R, Nakamura R, Forman SJ, Zaia JA, and Diamond DJ
- Subjects
- Adult, Antiviral Agents adverse effects, Antiviral Agents therapeutic use, Bone Marrow Transplantation adverse effects, CD8-Positive T-Lymphocytes metabolism, Cohort Studies, Cytokines metabolism, Cytomegalovirus physiology, Cytomegalovirus Infections drug therapy, Cytomegalovirus Infections physiopathology, Cytomegalovirus Infections transmission, Cytomegalovirus Vaccines, Disease Transmission, Infectious, Female, Graft Survival immunology, Hematologic Neoplasms blood, Hematologic Neoplasms immunology, Hematologic Neoplasms surgery, Humans, Immunity, Cellular, Male, Middle Aged, Peripheral Blood Stem Cell Transplantation adverse effects, Phosphoproteins immunology, Siblings, Transplantation, Homologous adverse effects, Treatment Outcome, Viral Matrix Proteins immunology, Virus Activation, Bone Marrow Transplantation statistics & numerical data, CD8-Positive T-Lymphocytes immunology, Cytomegalovirus isolation & purification, Cytomegalovirus Infections immunology, Peripheral Blood Stem Cell Transplantation statistics & numerical data, T-Cell Antigen Receptor Specificity, T-Lymphocyte Subsets immunology, Tissue Donors, Transplantation, Homologous statistics & numerical data
- Abstract
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-alpha (TNF-alpha), macrophage inflammatory protein-1beta (MIP-1beta), and CD107 in addition to interferon-gamma (IFN-gamma), compared with D(+)/R(+) recipients. Unlike monofunctional CD8(+) T cells secreting IFN-gamma, 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.
- Published
- 2009
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