Human cytomegalovirus-specific T cell reconstitution in young patients receiving T cell-depleted, allogeneic hematopoietic stem cell transplantation

Abstract

Background. Reconstitution of human cytomegalovirus (HCMV) T cell-specific immunity is of crucial relevance in patients receiving a hematopoietic stem cell transplant (HSCT). Scarce data on this subject are available for children receiving a T cell- depleted HSCT. Methods. We investigated HCMV-specific T cell recovery in 48 recipients of a T cell- depleted HSCT from a human leukocyte antigen (HLA)-disparate relative. Autologous HCMV-infected dendritic cells were used to stimulate HCMV-specific CD8+ and CD4+ T cells producing interferon-γ (IFN). Results. The 1-year cumulative incidence of both HCMV infection and specific T cell reconstitution was 83% among the 23 HCMV-seropositive patients and 4% and 8%, respectively, among the 25 HCMV-seronegative patients (P < .01). HCMV-specific T cell reconstitution was significantly delayed in patients receiving T cell- depleted grafts, compared with patients receiving unmanipulated HSCTs (median time to reconstitution, 75 vs. 47 days, respectively; P < .01). The median time from HCMV infection to immune recovery in recipients of T cell- depleted grafts was 47 days. Detection of HCMV-specific T cells correlated with control of HCMV infection. The number of residual T cells in the graft predicted earlier T cell recovery (P = .02). Conclusions. Latent HCMV in the recipient was the major cause of HCMV reactivation and also promoted specific T cell reconstitution in patients given a T cell- depleted HSCT from an HLA-disparate relative. Routine immunologic monitoring is valuable in identifying patients with early HCMV-specific T cell reconstitution. © 2009 by the Infectious Diseases Society of America.