First analysis of human herpesvirus 6T-cell responses: Specific boosting after HHV6 reactivation in stem cell transplantation recipients

Early human herpesvirus 6 (HHV6) reactivation after hematopoietic stem cell transplantation (HSCT) is associated with poor survival. We characterized HHV6 immuneresponses in HSCT patients during lymphopenia. Prospectively, HHV6 DNA-load was measured weekly by realtime-PCR. Numbers of IFNγ-producing HHV6-T-cells were retrospectively determined by enzyme-linked immunospot assay 2 months after HSCT. HHV6-specific T-cell proliferative capacity was analyzed with a newly developed assay using antigen-presenting autologous HHV6-infected PBMC. Fifty-six patients were included (median age 4.6 years; range 0.2–21.2 years). HHV6-reactivation occurred in 29/56 (52%) patients with a median time of 14 (range 1–41) days after HSCT. The median number of IFN-γ producing HHV6-specific T-cells at 2 months and the HHV6-specific CD8+ T-cell proliferative capacity at 6 months after HSCT was increased after HHV6-reactivation compared to non-reactivating patients (P = 0.006 and p = 0.019). In conclusion, HHV6-specific immuneresponses can be initiated during lymphopenia early after HSCT, which implicates a potential window for development of HHV6-specific (immuno)therapy.

► HHV6 reactivation is associated with poor survival after HSCT. ► No differences in overall T-cell reconstitution were found after viral reactivations. ► A model to analyze HHV6-specific T-cell proliferation in lymphopenia was developed. ► Increased CD8+ T-cell proliferation was found after HHV6 reactivation in lymphopenia. ► HHV6-specific immuneresponses can be initiated during lymphopenia.