Capture and generation of adenovirus specific T cells for adoptive immunotherapy.
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.
Chatziandreou
Ilenia
I
Molecular Immunology Unit, Institute of Child Health, University College London, London, UK.
Gilmour
Kimberly C
KC
McNicol
Anne-Marie
AM
Costabile
Maurizio
M
Sinclair
Joanna
J
Cubitt
David
D
Campbell
John D M
JD
Kinnon
Christine
C
Qasim
Waseem
W
Gaspar
H Bobby
HB
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
D000956:Antigens, Viral; D000939:Epitopes; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens