title: Selection of perforin expressing CD4+ adenovirus-specific T-cells with artificial antigen presenting cells.
abstract: Adenoviruses (HAdV) can cause life threatening infections, especially in paediatric patients after allogeneic stem cell transplantation (SCT). Yet, no effective antiviral medication is available. One treatment option is adoptive transfer of HAdV-specific T-cells from the graft donor into the patient. Especially CD4+ T-cells are critical to control HAdV infection. To allow for applicability of CD4+ T-cells in adoptive therapy, sufficient numbers of HAdV-specific T-cells with low levels of residual alloreactive T-cells are required. In this study, we explored the possibility to selectively expand and isolate functional HAdV-specific T-cells from PBMCs in response to 15-mer peptides using artificial antigen-presenting cells (aAPCs), composed of liposomes harbouring HAdV-peptide/HLA-Class-II complexes. HAdV-specific T-cells generated using this method produce mainly pro-inflammatory cytokines, express perforin and granzyme B, kill HAdV-infected cells effectively and are not alloreactive. Thus, the generation and isolation of HAdV-specific CD4+ T-cells seem a critical step towards specific adoptive therapy for HAdV infections after allogeneic SCT.
authors: Department of Paediatric Immunology and Haematology, University Medical Centre Utrecht, Wilhelmina Children's Hospital Utrecht, The Netherlands. l.m.haveman@amc.nl
authors: Lianne M
authors: LM
authors: Haveman
authors: Marc
authors: M
authors: Bierings
authors: Mark R
authors: MR
authors: Klein
authors: Jeffrey M
authors: JM
authors: Beekman
authors: Wilco
authors: W
authors: de Jager
authors: Wietse
authors: W
authors: Kuis
authors: Salvatore
authors: S
authors: Albani
authors: Berent J
authors: BJ
authors: Prakken
mesh_terms: D000258:Adenovirus Infections, Human / Q000276:immunology*; D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D053804:Granzymes / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D007959:Lymphocyte Culture Test, Mixed; D010455:Peptides / Q000494:pharmacology; D054353:Perforin / Q000276:immunology*
chemical_list: D000941:Antigens; D010455:Peptides; D054353:Perforin; D053804:Granzymes