CD8+ T-cell reconstitution in recipients of umbilical cord blood transplantation and characteristics associated with leukemic relapse

Abstract

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-A26-35 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.