Protective Immunity Transferred by Infusion of Cytomegalovirus-Specific CD8+ T Cells within Donor Grafts: Its Associations with Cytomegalovirus Reactivation Following Unmanipulated Allogeneic Hematopoietic Stem Cell Transplantation

Human cytomegalovirus (CMV)-specific cytotoxic T lymphocyte (CTL) immune response must be reconstituted for long-term protection against CMV relapse and disease in hematopoietic stem cell transplantation (HSCT) recipients. We phenotypically quantitated absolute numbers of CMV-pp65 peptide-specific CTLs (CTLCMV) in 50 related donor unmanipulated allografts infused into HLA-matched or -mismatched recipients and examined the incidence of CMV reactivation. High CTLCMV with terminally differentiated effector CD45RO-CD62L- cell (TEMRA) phenotype in the allografts were associated with reduced risk of CMV reactivation, in the presence of sufficient CD45RO+CD62L- cell (TEM) infusion (≥0.208 × 106/kg). Early after transplantation, there was significant expansion of CTLCMV with the central memory CD45RO+CD62L+ cell (TCM) phenotype when CMV was reactivated. The frequencies of CTLCMV TNaive (CD45RO-CD62L+), TCM, and TEM at day 90 posttransplantation and of CTLCMV TEMRA at day 60 posttransplantation were greater in recipients with higher infusions of CTLCMV TEMRA, suggesting protective immunity transferred by infusion of CTLCMV within allografts. Moreover, the majority of the CTLCMV identified in the recipients early after HSCT was of donor origin. Our findings support that measuring levels of CTLCMV and its subsets in the donor grafts and manipulating these cells early after transplantation may help control CMV reactivation, which is closely correlated with immune reconstitution and differentiation of CTLCMV subsets.