title: CMV-, EBV- and ADV-specific T cell immunity: screening and monitoring of potential third-party donors to improve post-transplantation outcome.
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.
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center (IFB-Tx), Hannover Medical School, Hannover, Germany.
authors.forename: Cinja
authors.initials: C
authors.lastname: Sukdolak
authors.forename: Sabine
authors.initials: S
authors.lastname: Tischer
authors.forename: Daria
authors.initials: D
authors.lastname: Dieks
authors.forename: Constanca
authors.initials: C
authors.lastname: Figueiredo
authors.forename: Lilia
authors.initials: L
authors.lastname: Goudeva
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Heuft
authors.forename: Murielle
authors.initials: M
authors.lastname: Verboom
authors.forename: Stephan
authors.initials: S
authors.lastname: Immenschuh
authors.forename: Albert
authors.initials: A
authors.lastname: Heim
authors.forename: Sylvia
authors.initials: S
authors.lastname: Borchers
authors.forename: Eva
authors.initials: E
authors.lastname: Mischak-Weissinger
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
authors.forename: Britta
authors.initials: B
authors.lastname: Maecker-Kolhoff
authors.forename: Britta
authors.initials: B
authors.lastname: Eiz-Vesper
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000328:Adult; D000368:Aged; D003587:Cytomegalovirus / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
keywords: Adenovirus; Adoptive immunotherapy; Antiviral T lymphocytes; Cytomegalovirus; Epstein-Barr virus; T cell therapy