title: Cytomegalovirus-Responsive CD8+T Cells Expand After Solid Organ Transplantation in the Absence of CMV Disease.
abstract: Cytomegalovirus (CMV) is a major cause of morbidity and mortality in solid organ transplant recipients. Approximately 60% of adults are CMV seropositive, indicating previous exposure. Following resolution of the primary infection, CMV remains in a latent state. Reactivation is controlled by memory T cells in healthy individuals; transplant recipients have reduced memory T cell function due to chronic immunosuppressive therapies. In this study, CD8+T cell responses to CMV polypeptides immediate-early-1 and pp65 were analyzed in 16 CMV-seropositive kidney and heart transplant recipients longitudinally pretransplantation and posttransplantation. All patients received standard of care maintenance immunosuppression, antiviral prophylaxis, and CMV viral load monitoring, with approximately half receiving T cell-depleting induction therapy. The frequency of CMV-responsive CD8+T cells, defined by the production of effector molecules in response to CMV peptides, increased during the course of 1 year posttransplantation. The increase commenced after the completion of antiviral prophylaxis, and these T cells tended to be terminally differentiated effector cells. Based on this small cohort, these data suggest that even in the absence of disease, antigenic exposure may continually shape the CMV-responsive T cell population posttransplantation.
authors.affiliation: Department of Medicine/Nephrology, Stanford University, Palo Alto, CA.
authors.forename: L E
authors.initials: LE
authors.lastname: Higdon
authors.affiliation: Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, PA.|Perelman School of Medicine, University of Pennsylvania, Renal Division, Philadelphia, PA.
authors.forename: J
authors.initials: J
authors.lastname: Trofe-Clark
authors.affiliation: Department of Medicine/Nephrology, Stanford University, Palo Alto, CA.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Cardiovascular Institute, Philadelphia, PA.
authors.forename: K B
authors.initials: KB
authors.lastname: Margulies
authors.affiliation: Stanford University, School of Medicine, Department of Pathology, Stanford, CA.
authors.forename: M K
authors.initials: MK
authors.lastname: Sahoo
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Infectious Diseases Division, Philadelphia, PA.
authors.forename: E
authors.initials: E
authors.lastname: Blumberg
authors.affiliation: Stanford University, School of Medicine, Department of Pathology, Stanford, CA.|Stanford University, School of Medicine, Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford, CA.
authors.forename: B A
authors.initials: BA
authors.lastname: Pinsky
authors.affiliation: Department of Medicine/Nephrology, Stanford University, Palo Alto, CA.|VA Palo Alto Health Care System, Palo Alto, CA.
authors.forename: J S
authors.initials: JS
authors.lastname: Maltzman
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D016027:Heart Transplantation; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D016030:Kidney Transplantation; D008137:Longitudinal Studies
keywords: T cell biology; basic (laboratory) research/science; flow cytometry; immune regulation; immunobiology; infection and infectious agents; infectious disease; viral: Cytomegalovirus (CMV)