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

Clin Immunol. 2012 Sep;144(3):179-89. doi: 10.1016/j.clim.2012.06.006. Epub 2012 Jun 30.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA, Viral / genetics
  • DNA, Viral / immunology
  • Female
  • Hematopoietic Stem Cell Transplantation / methods
  • Herpesvirus 6, Human / genetics
  • Herpesvirus 6, Human / immunology*
  • Humans
  • Infant
  • Interferon-gamma / immunology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Lymphopenia / immunology
  • Lymphopenia / virology
  • Male
  • Prospective Studies
  • Retrospective Studies
  • Roseolovirus Infections / genetics
  • Roseolovirus Infections / immunology*
  • Roseolovirus Infections / virology*
  • Stem Cells / immunology*
  • Virus Activation / genetics
  • Virus Activation / immunology
  • Young Adult

Substances

  • DNA, Viral
  • Interferon-gamma