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Impaired functionality of antiviral T cells in G-CSF mobilized stem cell donors: implications for the selection of CTL donor.
Bunse, Carola E Borchers, Sylvia Varanasi, Pavankumar R Tischer, Sabine Figueiredo, Constança Immenschuh, Stephan Kalinke, Ulrich Köhl, Ulrike Goudeva, Lilia Maecker-Kolhoff, Britta
Bunse, Carola E
Borchers, Sylvia
Varanasi, Pavankumar R
Tischer, Sabine
Figueiredo, Constança
Immenschuh, Stephan
Kalinke, Ulrich
Köhl, Ulrike
Goudeva, Lilia
Maecker-Kolhoff, Britta
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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.
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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 ONE
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1932-6203
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