title: A registry of HLA-typed donors for production of virus-specific CD4 and CD8 T lymphocytes for adoptive reconstitution of immune-compromised patients.
abstract: BACKGROUND
  Virus-specific CD4 and CD8 T lymphocytes from HLA-matched donors are effective for treatment and prophylaxis of viral infections in immune-compromised recipients of hematopoietic stem cell transplant recipients. Adoptive immune reconstitution is based on selection of specific T cells or on generation of specific T-cell lines from the graft donor. Unfortunately, the graft donor is not always immune to the relevant pathogen or the graft donor may not be available (registry-derived or cord blood donors).
  
  
  METHODS
  Since the possibility of using T cells from a third-party subject is now established, we screened potential donors for T-cell responses against cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus, the viruses most frequently targeted by adoptive immune reconstitution. Specific T-cell responses against viral antigens were analyzed in 111 donors using a miniaturized interferon-γ release assay.
  
  
  RESULTS
  Responders to CMV were 64%, to EBV 40%, and to adenovirus 51%. Simultaneous responders to the three viruses were 49%. CMV-specific CD4 and CD8 T-cell lines could be generated from 11 of 12 donors defined as positive responders according to the T-cell assay.
  
  
  CONCLUSIONS
  These data demonstrate that a large fraction of volunteers can be recruited in a donor registry for selection or expansion of virus specific T cells and that our T-cell assay predicts the donors' ability to give rise to established T-cell lines endowed with proliferative potential and effector function for adoptive immune reconstitution.
authors.affiliation: Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Li Pira
authors.forename: Federico
authors.initials: F
authors.lastname: Ivaldi
authors.forename: Nadia
authors.initials: N
authors.lastname: Starc
authors.forename: Fabiola
authors.initials: F
authors.lastname: Landi
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Sacchi
authors.forename: Gino
authors.initials: G
authors.lastname: Tripodi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manca
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D001681:Biological Assay / Q000379:methods; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D004266:DNA Virus Infections / Q000276:immunology / Q000628:therapy; D004267:DNA Viruses / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D000956:Antigens, Viral; D006680:HLA Antigens; C573415:IFNG protein, human; D007371:Interferon-gamma