title: Programmed Death 1 Expression on CD4+T Cells Predicts Mortality after Allogeneic Stem Cell Transplantation.
abstract: Excessive or persistent programmed death 1 (PD-1) expression on virus- or tumor-specific T cells during chronic viral infection or malignancy has been associated with impaired immune control. To assess the role of the PD-1 pathway in allogeneic stem cell transplantation (SCT), we examined PD-1 expression and maturation phenotype on T cells from 42 patients early (day 55 to 85) after cord blood (CB), matched unrelated donor, and matched related donor transplantation. Expression of PD-1 on CD4+T cells was significantly elevated in all transplantation types, with the highest level observed in CB subjects. Elevated PD-1 expression on CD4+T cells early after transplantation was observed in nonsurvivors (median, 40.2%; range, 15.1 to 86.1) compared with survivors (median, 23.6%; range, 8.4 to 55.2; P = .001), indicating its association with increased risk for mortality, especially with CB transplantations, where PD-1 was increased in nonsurvivors (median, 64.6%; range, 36.5 to 86.1) compared with survivors (median, 34.1%; range, 15.9 to 55.2; P = .01). Furthermore, T cell subset analysis revealed that PD-1 expression was further elevated on CD4+T central memory in nonsurvivors (median, 49.8%; range, 15.1 to 83.4) compared with survivors (median, 24.8%; range, 8.9 to 71.3; P = .002) and on T effector memory cells in nonsurvivors (median, 69.1%; range, 24.7 to 92.6) compared with survivors (median, 43.7%; range, 13.9 to 96.5; P = .0003). Our findings suggest that elevation of PD-1 expression on CD4+T cells is associated with mortality in CB and possibly all SCT recipients.
authors: School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Division of Hematology and Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors: Henning
authors: H
authors: Schade
authors: School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Division of Allergy and Clinical Immunology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors: Sharon
authors: S
authors: Sen
authors: Division of Allergy and Clinical Immunology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors: C Preston
authors: CP
authors: Neff
authors: School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Division of Allergy and Clinical Immunology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors: Brian M
authors: BM
authors: Freed
authors: Department of Pediatrics and Department of Biostatistics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors: Dexiang
authors: D
authors: Gao
authors: School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Division of Hematology and Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors: Jonathan A
authors: JA
authors: Gutman
authors: School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Division of Allergy and Clinical Immunology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Electronic address: brent.palmer@ucdenver.edu.
authors: Brent E
authors: BE
authors: Palmer
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D008875:Middle Aged; D009026:Mortality; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis*; D017741:Survivors; D016176:T-Lymphocyte Subsets / Q000737:chemistry; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Allogeneic stem cell transplantation; CD4(+) T cells; Cord blood; Programmed death 1 (PD-1) expression