Human Cytomegalovirus-Specific T Cell Reconstitution in Young Patients Receiving T Cell-Depleted, Allogeneic Hematopoietic Stem Cell Transplantation

J Infect Dis. 2009 Mar 15;199(6):829-36. doi: 10.1086/597123.

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-gamma (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / surgery*
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphocyte Depletion
  • Male
  • Recurrence
  • T-Lymphocytes / immunology*
  • Transplantation, Homologous
  • Young Adult