title: T-cell immunity to subclinical cytomegalovirus infection reduces cardiac allograft disease.
abstract: BACKGROUND
  Asymptomatic cytomegalovirus (CMV) replication is frequent after cardiac transplantation in recipients with pretransplantation CMV infection. How subclinical viral replication influences cardiac allograft disease remains poorly understood, as does the importance of T-cell immunity in controlling such replication.
  
  
  RESULTS
  Thirty-nine cardiac recipients who were pretransplantation CMV antibody positive were longitudinally studied for circulating CMV-specific CD4 and CD8 T-cell responses, CMV viral load in blood neutrophils, and allograft rejection during the first posttransplantation year. Nineteen of these recipients were also analyzed for changes of coronary artery intimal, lumen, and whole-vessel area. All recipients received early prophylactic therapy with ganciclovir. No recipients developed overt CMV disease. Those with detectable levels of CMV-specific CD4 T cells in the first month after transplantation were significantly protected from high mean and peak posttransplantation viral load (P<0.05), acute rejection (P<0.005), and loss of allograft coronary artery lumen (P<0.05) and of whole-vessel area (P<0.05) compared with those who lacked this immune response. The losses of lumen and vessel area were both significantly correlated with the time after transplantation at which a CD4 T-cell response was first detected (P<0.05) and with the cumulative graft rejection score (P<0.05).
  
  
  CONCLUSIONS
  The early control of subclinical CMV replication after transplantation by T-cell immunity may limit cardiac allograft rejection and vascular disease. Interventions to increase T-cell immunity might be clinically useful in limiting these adverse viral effects.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5164, USA.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Tu
authors.forename: Luciano
authors.initials: L
authors.lastname: Potena
authors.forename: Pamela
authors.initials: P
authors.lastname: Stepick-Biek
authors.forename: Lanxiang
authors.initials: L
authors.lastname: Liu
authors.forename: Kira Y
authors.initials: KY
authors.lastname: Dionis
authors.forename: Helen
authors.initials: H
authors.lastname: Luikart
authors.forename: William F
authors.initials: WF
authors.lastname: Fearon
authors.forename: Tyson H
authors.initials: TH
authors.lastname: Holmes
authors.forename: Clifford
authors.initials: C
authors.lastname: Chin
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Valantine
authors.forename: Edward S
authors.initials: ES
authors.lastname: Mocarski
authors.forename: David B
authors.initials: DB
authors.lastname: Lewis
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003324:Coronary Artery Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology; D003587:Cytomegalovirus / Q000276:immunology / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir