Immunotherapeutic strategies to prevent and treat human herpesvirus 6 reactivation after allogeneic stem cell transplantation

Blood. 2013 Jan 3;121(1):207-18. doi: 10.1182/blood-2012-05-430413. Epub 2012 Nov 14.


Human herpesvirus (HHV) 6 causes substantial morbidity and mortality in the immunocompromised host and has no approved therapy. Adoptive transfer of virus specific T cells has proven safe and apparently effective as prophylaxis and treatment of other virus infections in immunocompromised patients; however, extension to subjects with HHV6 has been hindered by the paucity of information on targets of cellular immunity. We now characterize the cellular immune response from 20 donors against 5 major HHV6B antigens predicted to be immunogenic and define a hierarchy of immunodominance of antigens based on the frequency of responding donors and the magnitude of the T-cell response. We identified specific epitopes within these antigens and expanded the HHV6 reactive T cells using a GMP-compliant protocol. The expanded population comprised both CD4(+) and CD8(+) T cells that were able to produce multiple effector cytokines and kill both peptide-loaded and HHV6B wild-type virus-infected target cells. Thus, we conclude that adoptive T-cell immunotherapy for HHV6 is a practical objective and that the peptide and epitope tools we describe will allow such cells to be prepared, administered, and monitored in human subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured / immunology
  • Coculture Techniques
  • Cytomegalovirus / immunology
  • Cytotoxicity, Immunologic
  • Forkhead Transcription Factors / analysis
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Herpesvirus 6, Human / immunology*
  • Herpesvirus 6, Human / isolation & purification
  • Herpesvirus 6, Human / physiology
  • Humans
  • Immunocompromised Host
  • Immunodominant Epitopes / immunology
  • Immunotherapy, Adoptive*
  • Lymphocyte Activation
  • Monocytes / immunology
  • Roseolovirus Infections / prevention & control
  • Roseolovirus Infections / therapy*
  • T-Cell Antigen Receptor Specificity
  • Transplantation, Homologous / adverse effects*
  • Virus Activation* / immunology


  • Antigens, Viral
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunodominant Epitopes