Longitudinal assessment of cytomegalovirus (CMV)-specific immune responses in liver transplant recipients at high risk for late CMV disease.
Cytomegalovirus (CMV)-seronegative recipients (R(-)) of a liver transplant from CMV-positive donors (D(+)) are at high risk for developing late CMV disease after discontinuation of antiviral prophylaxis. Levels of viremia and CMV-specific interferon (IFN)- gamma -producing CD4(+) and IFN- gamma -producing CD8(+) T cell responses were prospectively measured from discontinuation of antiviral prophylaxis until 1 year after transplantation in 17 consecutive D(+)/R(-) patients. CMV loads of >1000 copies/mL were strongly associated with CMV disease in the 6 symptomatic patients. Despite immunosuppression, broadly diverse T cells specific for CMV lysate or peptide libraries spanning pp65 and immediate early (IE) 1 immunodominant CMV antigens developed in all patients. A vigorous CD8(+) T cell response to pp65 and IE1 antigens characterized the D(+)/R(-) cohort. Unexpectedly, none of these responses were predictive of CMV disease or viremia. No significant lymphopenia or functional impairment of CMV-specific T cells was detected in the symptomatic patients, whose morbidity was resolved after antiviral treatment while measurable CMV immunity was maintained during the 1-year observation period.
La Rosa
Corinna
C
Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. ddiamond@coh.org
Limaye
Ajit P
AP
Krishnan
Aparna
A
Longmate
Jeff
J
Diamond
Don J
DJ
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism; D012307:Risk Factors; D000077562:Valganciclovir; D014763:Viral Matrix Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014766:Viremia
D000998:Antiviral Agents; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma; D000077562:Valganciclovir; D015774:Ganciclovir