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- 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; 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.
- Subjects
ANTIVIRAL agents; T cells; GRANULOCYTE-colony stimulating factor; STEM cell transplantation; IMMUNE reconstitution inflammatory syndrome; IMMUNOLOGICAL adjuvants; HLA histocompatibility antigens
- Publication
PLoS ONE, 2013, Vol 8, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0077925