Impaired functionality of antiviral T cells in G-CSF mobilized stem cell donors: implications for the selection of CTL donor.

2.50
Hdl Handle:
http://hdl.handle.net/10033/315887
Title:
Impaired functionality of antiviral T cells in G-CSF mobilized stem cell donors: implications for the selection of CTL donor.
Authors:
Bunse, Carola E; Borchers, Sylvia; Varanasi, Pavankumar R; Tischer, Sabine; Figueiredo, Constança; Immenschuh, Stephan; Kalinke, Ulrich ( 0000-0003-0503-9564 ) ; Köhl, Ulrike; Goudeva, Lilia; Maecker-Kolhoff, Britta; Ganser, Arnold; Blasczyk, Rainer; Weissinger, Eva M; Eiz-Vesper, Britta
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.
Affiliation:
HZI Außenstelle TWINCORE, Feodor-Lynen-Str. 7, D-30625 Hannover
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 ONE
Publisher:
PLOS
Journal:
PloS one
Issue Date:
2013
URI:
http://hdl.handle.net/10033/315887
DOI:
10.1371/journal.pone.0077925
PubMed ID:
24324576
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorBunse, Carola Een
dc.contributor.authorBorchers, Sylviaen
dc.contributor.authorVaranasi, Pavankumar Ren
dc.contributor.authorTischer, Sabineen
dc.contributor.authorFigueiredo, Constançaen
dc.contributor.authorImmenschuh, Stephanen
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorKöhl, Ulrikeen
dc.contributor.authorGoudeva, Liliaen
dc.contributor.authorMaecker-Kolhoff, Brittaen
dc.contributor.authorGanser, Arnolden
dc.contributor.authorBlasczyk, Raineren
dc.contributor.authorWeissinger, Eva Men
dc.contributor.authorEiz-Vesper, Brittaen
dc.date.accessioned2014-04-16T09:56:28Zen
dc.date.available2014-04-16T09:56:28Zen
dc.date.issued2013en
dc.identifier.citationImpaired functionality of antiviral T cells in G-CSF mobilized stem cell donors: implications for the selection of CTL donor. 2013, 8 (12):e77925 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid24324576en
dc.identifier.doi10.1371/journal.pone.0077925en
dc.identifier.urihttp://hdl.handle.net/10033/315887en
dc.description.abstractAdoptive 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.en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsArchived with thanks to PloS oneen
dc.titleImpaired functionality of antiviral T cells in G-CSF mobilized stem cell donors: implications for the selection of CTL donor.en
dc.typeArticleen
dc.contributor.departmentHZI Außenstelle TWINCORE, Feodor-Lynen-Str. 7, D-30625 Hannoveren
dc.identifier.journalPloS oneen
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