CMV-, EBV- and ADV-specific T cell immunity: screening and monitoring of potential third-party donors to improve post-transplantation outcome

Biol Blood Marrow Transplant. 2013 Oct;19(10):1480-92. doi: 10.1016/j.bbmt.2013.07.015. Epub 2013 Jul 23.

Abstract

Adoptive immunotherapy with virus-specific T lymphocytes can efficiently reconstitute antiviral immunity against cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) without causing acute toxicity or increasing the risk of graft-versus-host disease. To gain insight into antiviral T cell repertoires and to identify the most efficient antigens for immunotherapy, the frequencies of CMV-, EBV- and ADV-specific T cells in 204 HLA-typed healthy donors were assessed using viral peptides and peptide pools. Confirmatory testing for CMV serology by Western blot technique revealed 19 of 143 (13%) false-positive results. We observed highly significant individual and overall differences in T cell frequencies against CMV, EBV, and ADV antigens, whereas antigen-specific T cells were detected in 100% of CMV- seropositive donors, 73% of EBV- seropositive donors, and 73% of ADV-seropositive donors. At least 124 (61%) potential T cell donors were identified for each virus. Among the tested antigens, frequencies for CMVpp65 and EBVBZLF1 peptide pools were highest. Short-term in vitro peptide stimulation revealed that a donor response to a certain ADV- and EBV-derived peptide may not be determined without prior stimulation. A modified granzyme B ELISpot was used to detect T cell specificity and alloreactivity. Treatment with allogeneic virus-specific cytotoxic T lymphocytes from seropositive third-party donors may be a feasible therapeutic option for infections following cord-blood stem cell transplantation or hematopoietic stem cell transplantation from virus-seronegative donors.

Keywords: Adenovirus; Adoptive immunotherapy; Antiviral T lymphocytes; Cytomegalovirus; Epstein-Barr virus; T cell therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / immunology*
  • Adult
  • Aged
  • Cytomegalovirus / immunology*
  • Epstein-Barr Virus Infections / immunology*
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Male
  • Middle Aged
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transplantation Conditioning / methods*
  • Treatment Outcome
  • Young Adult