T-cell immunity to subclinical cytomegalovirus infection reduces cardiac allograft disease.
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.
Tu
Wenwei
W
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5164, USA.
Potena
Luciano
L
Stepick-Biek
Pamela
P
Liu
Lanxiang
L
Dionis
Kira Y
KY
Luikart
Helen
H
Fearon
William F
WF
Holmes
Tyson H
TH
Chin
Clifford
C
Cooke
John P
JP
Valantine
Hannah A
HA
Mocarski
Edward S
ES
Lewis
David B
DB
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
D000998:Antiviral Agents; D015774:Ganciclovir