title: CD8(+) T-cell reconstitution in recipients of umbilical cord blood transplantation and characteristics associated with leukemic relapse.
abstract: Recipients of umbilical cord blood (UCB) transplantation (UCBT) face a high risk of morbidity and mortality related to opportunistic infections (OI) and leukemic relapse. To understand the molecular basis of these UCBT-related complications, the characteristics of UCB-derived antigen-specific CD8(+) T cells were examined in a group of pediatric UCBT recipients. Compared with the UCB graft inoculum and the late post-UCBT period (12-36 months), declining clonal diversity of UCB-derived CD8(+) T cells specific for the Melan-A(26-35) A27L peptide and high frequencies of PD-1-expressing CD8(+) T cells were observed in the first 3 months after UCBT, a period during which OIs are most frequent. The CD8(+) T-cell compartment predominantly comprised CD45RA(+) CCR7(-) terminally differentiated effector-memory T cells until 6 months after UCBT, at which time the polyfunctionality of antigen-specific CD8(+) T cells was reestablished. Finally, the frequency of PD-1(+) CD8(+) T cells was significantly higher in subjects who subsequently experienced leukemic relapse. This study informs the biologic properties of UCB-derived CD8(+) T cells and provides a rationale for the characteristics of UCBT in terms of immune reconstitution and OI. These results also suggest that the elevated frequency of PD-1(+) CD8(+) T cells could be associated with leukemic relapse in pediatric UCBT recipients.
authors.affiliation: Unité d'Immunopathologie Virale, Centre de Recherche du CHU Sainte-Justine, Montreal, QC, Canada.
authors.forename: Natacha
authors.initials: N
authors.lastname: Merindol
authors.forename: Martin A
authors.initials: MA
authors.lastname: Champagne
authors.forename: Michel
authors.initials: M
authors.lastname: Duval
authors.forename: Hugo
authors.initials: H
authors.lastname: Soudeyns
mesh_terms: D000293:Adolescent; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005312:Fetal Blood / Q000637:transplantation*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000517:prevention & control* / Q000601:surgery*; D058965:MART-1 Antigen / Q000032:analysis / Q000276:immunology; D008297:Male; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis / Q000276:immunology; D012008:Recurrence
chemical_list: D058965:MART-1 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor