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Capture and generation of adenovirus specific T cells for adoptive immunotherapy.
- Source :
-
British journal of haematology [Br J Haematol] 2007 Jan; Vol. 136 (1), pp. 117-26. Date of Electronic Publication: 2006 Nov 08. - Publication Year :
- 2007
-
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.
- Subjects :
- Adult
Antigens, Viral
Cell Proliferation
Cell Separation methods
Cytotoxicity Tests, Immunologic
Dendritic Cells immunology
Epitopes
Flow Cytometry
Humans
Immunophenotyping
Interferon-gamma immunology
Leukocyte Common Antigens immunology
Lymphocyte Culture Test, Mixed
Adenovirus Infections, Human immunology
Adenoviruses, Human
CD4-Positive T-Lymphocytes immunology
Immunotherapy, Adoptive
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1048
- Volume :
- 136
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 17092305
- Full Text :
- https://doi.org/10.1111/j.1365-2141.2006.06386.x