title: Capture and generation of adenovirus specific T cells for adoptive immunotherapy.
abstract: Adenoviral infections represent a major cause of morbidity and mortality following haematopoietic stem cell transplantation. Current anti-viral agents are virostatic and it is evident that elimination of adenovirus (ADV) infection is only achieved by recovery of cellular immunity. Using an interferon-gamma (IFN-gamma) secretion and capture assay to isolate ADV-specific T cells, followed by a 2 week expansion and restimulation protocol, we generated ADV T cells that may be used for cellular immunotherapy. In contrast to virus-specific T cells for cytomegalovirus or Epstein-Barr virus, the ADV response was dominated by CD4(+) T cells and the majority of captured cells exhibited an effector/memory immunophenotype. Highly specific antigen responses were demonstrated by intracellular IFN-gamma expression and cytotoxicity assays when the expanded cells underwent restimulation with ADV-pulsed target cells. Although T cells were initially generated in response to ADV species C, the expanded populations also showed strong activity against ADV species B, suggesting cross-reactivity across ADV species; a finding that has important clinical consequences in the paediatric setting, where the majority of infections are caused by ADV type B and C. The protocols can be readily translated to generate ADV-specific T cells suitable for clinical use and offer an effective immunotherapeutic strategy to control ADV infection.
authors.affiliation: Molecular Immunology Unit, Institute of Child Health, University College London, London, UK.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Chatziandreou
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Gilmour
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: McNicol
authors.forename: Maurizio
authors.initials: M
authors.lastname: Costabile
authors.forename: Joanna
authors.initials: J
authors.lastname: Sinclair
authors.forename: David
authors.initials: D
authors.lastname: Cubitt
authors.forename: John D M
authors.initials: JD
authors.lastname: Campbell
authors.forename: Christine
authors.initials: C
authors.lastname: Kinnon
authors.forename: Waseem
authors.initials: W
authors.lastname: Qasim
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
mesh_terms: D000258:Adenovirus Infections, Human / Q000276:immunology*; D000260:Adenoviruses, Human; D000328:Adult; D000956:Antigens, Viral; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens