Human AdV-specific T cells: persisting in vitro functionality despite lethal irradiation.
Viral infections caused by human adenovirus (HAdV) or CMV remain life-threatening complications in immunocompromised patients undergoing allogeneic hematopoietic stem cell transplantation. Adoptive immunotherapy with virus-specific T cells showed impressive clinical results without or with only mild GvHD. However, because of high costs and high regulatory barriers, these protocols are accessible to only a few centers. The infusion of unmanipulated donor lymphocytes (DLIs) that contain virus-specific T cells is not feasible because of the risk of GvHD. Reports about three patients treated with irradiated granulocytes or DLIs that potentially comprised virus-specific T cells discussed an active role of virus-specific lymphocytes despite irradiation, but real evidence could not be provided. Therefore, we tested the effect of irradiation on HAdV-specific T cells, which had been expanded in vitro, by stimulating PBMCs with HAdV-peptide pools and IL-15 for 12 days. Cells were then irradiated with 30 Gy, as performed for normal granulocyte concentrates. Cell viability and polyfunctional activity were determined by flow cytometry. Even 48 h after irradiation, 15.6% of expanded HAdV-specific T cells were apparently viable and cytolytically active. Although the in vivo antiviral activity was not tested, these data support earlier assumptions about the potential role of irradiated cells in patients.
Department of Clinical Cell Biology and FACS Core Unit, Children's Cancer Research Institute (CCRI), Vienna, Austria.
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R
Geyeregger
Department of Clinical Cell Biology and FACS Core Unit, Children's Cancer Research Institute (CCRI), Vienna, Austria.
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C
Freimüller
Department of Clinical Cell Biology and FACS Core Unit, Children's Cancer Research Institute (CCRI), Vienna, Austria.
J
J
Stemberger
Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
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G
Fischer
Department of Apheresis/Infusion Unit, St. Anna Children's Hospital, Vienna, Austria.
V
V
Witt
1] Department of Clinical Cell Biology and FACS Core Unit, Children's Cancer Research Institute (CCRI), Vienna, Austria [2] Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
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G
Fritsch
D000258:Adenovirus Infections, Human / Q000276:immunology / Q000628:therapy* / Q000821:virology; D000260:Adenoviruses, Human / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects*; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous