Retrovirus-mediated gene transfer in polyclonal T cells results in lower apoptosis and enhanced ex vivo cell expansion of CMV-reactive CD8 T cells as compared with EBV-reactive CD8 T cells.

Details

Serval ID
serval:BIB_52FAFEC5B2B3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Retrovirus-mediated gene transfer in polyclonal T cells results in lower apoptosis and enhanced ex vivo cell expansion of CMV-reactive CD8 T cells as compared with EBV-reactive CD8 T cells.
Journal
Blood
Author(s)
Sauce D., Rufer N., Mercier P., Bodinier M., Rémy-Martin J.P., Duperrier A., Ferrand C., Hervé P., Romero P., Lang F., Tiberghien P., Robinet E.
ISSN
0006-4971
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
102
Number
4
Pages
1241-8
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
To modulate alloreactivity after hematopoietic stem cell transplantation, "suicide" gene-modified donor T cells (GMCs) have been administered with an allogeneic T-cell-depleted marrow graft. We previously demonstrated that such GMCs, generated after CD3 activation, retrovirus-mediated transduction, and G418 selection, had an impaired Epstein-Barr virus (EBV) reactivity, likely to result in an altered control of EBV-induced lymphoproliferative disease. To further characterize the antiviral potential of GMCs, we compared the frequencies of cytomegalovirus (CMV)-specific CD8+ T (CMV-T) cells and EBV-specific CD8+ T (EBV-T) cells within GMCs from CMV- and EBV-double seropositive donors. Unlike anti-EBV responses, the anti-CMV responses were not altered by GMC preparation. During the first days of culture, CMV-T cells exhibited a lower level of CD3-induced apoptosis than did EBV-T cells. In addition, the CMV-T cells escaping initial apoptosis subsequently underwent a higher expansion rate than EBV-T cells. The differential early sensitivity to apoptosis could be in relation to the "recent activation" phenotype of EBV-T cells as evidenced by a higher level of CD69 expression. Furthermore, EBV-T cells were found to have a CD45RA-CD27+CCR7- effector memory phenotype, whereas CMV-T cells had a CD45RA+CD27-CCR7- terminal effector phenotype. Such differences could be contributive, because bulk CD8+CD27- cells had a higher expansion than did bulk CD8+CD27+ cells. Overall, ex vivo T-cell culture differentially affects apoptosis, long-term proliferation, and overall survival of CMV-T and EBV-T cells. Such functional differences need to be taken into account when designing cell and/or gene therapy protocols involving ex vivo T-cell manipulation.
Keywords
Antigens, CD, Antigens, CD3, Antigens, Differentiation, T-Lymphocyte, Apoptosis, CD8-Positive T-Lymphocytes, Cell Transformation, Viral, Cells, Cultured, Cytomegalovirus, Gene Transfer Techniques, Herpesvirus 4, Human, Humans, Immunophenotyping, Lymphocyte Activation, Oligopeptides, Phosphoproteins, Retroviridae, Viral Matrix Proteins
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:27
Last modification date
20/08/2019 14:08
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