title: Increased programmed death-1 molecule expression in cytomegalovirus disease and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation.
abstract: To study the role of the programmed death-1 molecule (PD-1) in cytomegalovirus (CMV) infection and disease after allogeneic hematopoietic cell transplantation (HCT), 206 subjects were followed prospectively for immune response to CMV and assigned to 3 groups based on CMV outcome. The subjects were analyzed retrospectively for PD-1 expression in cryopreserved CD4+ and CD8+T cells collected at days 40, 90, 120, 150, 180, and 360 posttransplantation. HCT recipients with CMV disease (n=14) were compared with recipients with prolonged CMV infection, but no CMV disease (median duration of infection, 3 months; n=14) and with controls with no CMV infection who received similar transplants (n=22). The CMV disease group had a significantly higher mean fluorescein intensity of PD-1 in CD4+ (P < .05) and CD8+ (P < .05) lymphocytes at all time points studied. PD-1 expression also was significantly elevated in those with severe acute graft-versus-host disease (aGVHD), including the no-viremia group. The data suggest that PD-1 is induced by aGVHD even in the absence of CMV infection. This enhanced PD-1 expression during severe aGVHD and with CMV reactivation could explain the known role of aGVHD as a risk factor for CMV disease.
authors.affiliation: CMV Laboratory, Department of Virology, City of Hope, Duarte, California, USA.
authors.forename: Ghislaine M
authors.initials: GM
authors.lastname: Gallez-Hawkins
authors.forename: Lia
authors.initials: L
authors.lastname: Thao
authors.forename: Joycelynne
authors.initials: J
authors.lastname: Palmer
authors.forename: Andrew
authors.initials: A
authors.lastname: Dagis
authors.forename: Xiuli
authors.initials: X
authors.lastname: Li
authors.forename: Anne E
authors.initials: AE
authors.lastname: Franck
authors.forename: Bernard
authors.initials: B
authors.lastname: Tegtmeier
authors.forename: Simon F
authors.initials: SF
authors.lastname: Lacey
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: John A
authors.initials: JA
authors.lastname: Zaia
mesh_terms: D000208:Acute Disease; D015703:Antigens, CD / Q000096:biosynthesis*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000378:metabolism* / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D061026:Programmed Cell Death 1 Receptor; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor