title: Programmed death-1 expression in liver transplant recipients as a prognostic indicator of cytomegalovirus disease.
abstract: Immunological parameters that distinguish solid-organ transplant (SOT) recipients at risk for life-threatening cytomegalovirus (CMV) disease are being actively pursued to aid posttransplant management. A candidate marker is programmed death (PD)-1 receptor, whose overexpression has been associated with disease progression during persistent viral infections. To determine whether levels of this negative regulator of T cell activity are altered in SOT recipients with symptoms of CMV disease, a comparative PD-1 expression analysis was done in healthy, CMV-positive individuals and in liver transplant recipients. PD-1 levels were measured among the total population of CD8(+) and CD8(+) T cells binding to CMV-specific major histocompatibility complex class I tetramers. Minimal PD-1 expression was found in the healthy, CMV-positive cohort, and symptomatic SOT recipients had significantly higher PD-1 levels. PD-1 up-regulation was significantly associated with incipient and overt CMV disease and with viremia. Our findings suggest that PD-1 could be developed as a prognostic tool to predict CMV disease and guide therapeutic interventions.
authors.affiliation: Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
authors.forename: Corinna
authors.initials: C
authors.lastname: La Rosa
authors.forename: Aparna
authors.initials: A
authors.lastname: Krishnan
authors.forename: Jeff
authors.initials: J
authors.lastname: Longmate
authors.forename: Joy
authors.initials: J
authors.lastname: Martinez
authors.forename: Pooja
authors.initials: P
authors.lastname: Manchanda
authors.forename: Simon F
authors.initials: SF
authors.lastname: Lacey
authors.forename: Ajit P
authors.initials: AP
authors.lastname: Limaye
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D016022:Case-Control Studies; D003586:Cytomegalovirus Infections / Q000503:physiopathology*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008137:Longitudinal Studies; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor; D015854:Up-Regulation; D014766:Viremia / Q000097:blood / Q000503:physiopathology*
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor