Impaired functionality of antiviral T cells in G-CSF mobilized stem cell donors: implications for the selection of CTL donor.
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Authors
Bunse, Carola EBorchers, Sylvia
Varanasi, Pavankumar R
Tischer, Sabine
Figueiredo, Constança
Immenschuh, Stephan
Kalinke, Ulrich
Köhl, Ulrike
Goudeva, Lilia
Maecker-Kolhoff, Britta
Ganser, Arnold
Blasczyk, Rainer
Weissinger, Eva M
Eiz-Vesper, Britta
Issue Date
2013
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Show full item recordAbstract
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.Citation
Impaired functionality of antiviral T cells in G-CSF mobilized stem cell donors: implications for the selection of CTL donor. 2013, 8 (12):e77925 PLoS ONEAffiliation
HZI Außenstelle TWINCORE, Feodor-Lynen-Str. 7, D-30625 HannoverPublisher
PLOSJournal
PloS onePubMed ID
24324576Type
ArticleLanguage
enISSN
1932-6203ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0077925
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