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Ex vivo generation of human cytomegalovirus-specific cytotoxic T cells by peptide-pulsed dendritic cells.
- Source :
- British Journal of Haematology; Apr2001, Vol. 113 Issue 1, p231-239, 9p, 1 Diagram, 3 Graphs
- Publication Year :
- 2001
-
Abstract
- Adoptive transfer of donor-derived human cytomegalovirus (HCMV)-specific T-cell clones can restore protective immunity after stem cell transplantation. Ex vivo induction of HCMV-specific T cells using HCMV-infected fibroblasts as stimulator cells confines this approach to HCMV-seropositive donors and requires the presence of infectious virus during the stimulation procedure. In this study, we describe a potential alternative strategy to generate HCMV-specific T cells ex vivo for adoptive immunotherapy. Generation of HCMV-specific cytotoxic T lymphocytes (CTLs) ex vivo was investigated using peptide-pulsed dendritic cells as antigen-presenting cells. HCMV-specific T cells were generated and sufficiently expanded for adoptive immunotherapy in 6 out of 14 HCMV-seropositive and 2 out of 11 HCMV-seronegative donors. The CTLs recognized HCMV-infected autologous fibroblasts. No lysis was observed with either non-infected autologous or HLA-mismatched infected fibroblasts. Staining with tetrameric HLA/peptide complexes revealed significant enrichment for peptide-specific T cells of up to 28% and > 90% of CD8<superscript>+</superscript> T cells after three and five specific stimulations respectively. In addition, the expansion rates indicated that ex vivo generation of > 1 × 10<superscript>9</superscript> HCMV-specific T cells was possible after 6–7 weeks when cultures were initiated with 1–5 × 10<superscript>6</superscript> responder cells. Thus, the approach with peptide-pulsed DCs to generate HCMV-specific CTLs is feasible for clinical application after allogeneic stem cell transplantation. [ABSTRACT FROM AUTHOR]
- Subjects :
- CYTOMEGALOVIRUS diseases
IMMUNOTHERAPY
T cells
THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 00071048
- Volume :
- 113
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- British Journal of Haematology
- Publication Type :
- Academic Journal
- Accession number :
- 4534504
- Full Text :
- https://doi.org/10.1046/j.1365-2141.2001.02681.x