Epstein-Barr Virus Reactivation does not Impact Total T-Cell Reconstitution but is associated with Decreased Functional T Cells after Stem Cell Transplantation

Abstract

Epstein-Barr virus reactivations are frequently observed after allogeneic stem cell transplantation (SCT). We investigated the role of total as well as EBV-specific T-cell reconstitution in relation to onset and severity of EBV reactivation. To this end, 116 patients were prospectively sampled for viral load and absolute T-cell numbers weekly post-SCT during the first 3 months and thereafter monthly until 6 months post-SCT. In addition, we retrospectively analysed EBV-specific T-cell responses in 12 patients during the first year after SCT.In contrast to the general belief, we found that early T-cell reconstitution after SCT does not play a role in the onset of EBV reactivation as numbers of CD4+ and CD8+ T cells during the first 3 months post SCT are similar in patients with or without viral reactivation. However, functional T-cell responses after non-specific in-vitro restimulation were impaired in patients with high-level EBV-reactivation. Although EBV-specific CD8+ T-cell responses were readily detected from 2 months onward, EBV-specific CD4+ T cells remained low throughout followup, and especially EBNA-1-specific CD4+ T cells did not normalize to healthy control levels one year post-SCT.In conclusion, EBV-reactivation does not influence total T-cell reconstitution, but functional capacity is impaired in patients with high-level EBV-reactivation.