title: Impaired functionality of antiviral T cells in G-CSF mobilized stem cell donors: implications for the selection of CTL donor.
abstract: Adoptive transfer of antiviral T cells enhances immune reconstitution and decreases infectious complications after stem cell transplantation. Information on number and function of antiviral T cells in stem cell grafts is scarce. We investigated (1) immunomodulatory effects of G-CSF on antiviral T cells, (2) the influence of apheresis, and (3) the optimal time point to collect antiviral cells. CMV-, EBV- and ADV-specific T cells were enumerated in 170 G-CSF-mobilized stem cell and 24 non-mobilized platelet donors using 14 HLA-matched multimers. T-cell function was evaluated by IFN-γ ELISpot and granzyme B secretion. Immunophenotyping was performed by multicolor flow cytometry. G-CSF treatment did not significantly influence frequency of antiviral T cells nor their in vitro expansion rate upon antigen restimulation. However, T-cell function was significantly impaired, as expressed by a mean reduction in secretion of IFN-γ (75% in vivo, 40% in vitro) and granzyme B (32% target-independent, 76% target-dependent) as well as CD107a expression (27%). Clinical follow up data indicate that the first CMV-reactivation in patients and with it the need for T-cell transfer occurs while the donor is still under the influence of G-CSF. To overcome these limitations, T-cell banking before mobilization or recruitment of third party donors might be an option to optimize T-cell production.
authors: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany ; Integrated Research and Treatment Centre Transplantation, IFB-Tx, Hannover Medical School, Hannover, Germany.
authors: Carola E
authors: CE
authors: Bunse
authors: Sylvia
authors: S
authors: Borchers
authors: Pavankumar R
authors: PR
authors: Varanasi
authors: Sabine
authors: S
authors: Tischer
authors: Constança
authors: C
authors: Figueiredo
authors: Stephan
authors: S
authors: Immenschuh
authors: Ulrich
authors: U
authors: Kalinke
authors: Ulrike
authors: U
authors: Köhl
authors: Lilia
authors: L
authors: Goudeva
authors: Britta
authors: B
authors: Maecker-Kolhoff
authors: Arnold
authors: A
authors: Ganser
authors: Rainer
authors: R
authors: Blasczyk
authors: Eva M
authors: EM
authors: Weissinger
authors: Britta
authors: B
authors: Eiz-Vesper
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D019264:Adoptive Transfer; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D053804:Granzymes / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014019:Tissue Donors; D014764:Viral Proteins
chemical_list: D015415:Biomarkers; D014764:Viral Proteins; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D053804:Granzymes