Epitopes described in "Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants."

Article Authors:Georg Rauser; Hermann Einsele; Christian Sinzger; Dorothee Wernet; Gabriele Kuntz; Mario Assenmacher; John D M Campbell; Max S Topp
Article Title:Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants.
Reference Detail
Reference ID:1020091
Abstract:Adoptive transfer of cytomegalovirus (CMV)-specific T cells can restore long-lasting, virus-specific immunity and clear CMV viremia in recipients of allogeneic stem cell transplants if CD4(+) and CD8(+) CMV-specific T cells are detected in the recipient after transfer. Current protocols for generating virus-specific T cells use live virus, require leukapheresis of the donor, and are time consuming. To circumvent these limitations, a clinical-scale protocol was developed to generate CMV-specific T cells by using autologous cellular and serum components derived from a single 500-mL blood draw. CMV-specific T cells were stimulated simultaneously with CMV-specific major histocompatibility complex class I (MHC I)- restricted peptides and CMV antigen. Activated T cells were isolated with the interferon-gamma (IFN-gamma) secretion assay and expanded for 10 days. In 8 randomly selected, CMV-seropositive donors, 1.34 x 10(8) combined CD4(+) and CD8(+) CMV-specific T cells, on average, were generated, as determined by antigen-triggered IFN-gamma production. CMV-infected fibroblasts were efficiently lysed by the generated T cells, and CMV-specific CD4(+) and CD8(+) T cells expanded if they were stimulated with natural processed antigen. On the other hand, CD4(+) and CD8(+) T cell-mediated alloreactivity of generated CMV-specific T-cell lines was reduced compared with that of the starting population. In conclusion, the culture system developed allowed the rapid generation of allodepleted, highly enriched, combined CD4(+) and CD8(+) CMV-specific T cells under conditions mimicking good manufacturing practice.
Affiliations:Medizinische Klinik II, Eberhard-Karls-Universit├Ąt, Tuebingen, Germany.
Reference Type:Literature
PubMed ID:14670917
Journal Volume:103
Article Pages:3565-72
Journal ISSN:0006-4971
Article Chemical List:Antigens, Viral;Peptides
Article MeSH List:Adoptive Transfer(methods); Antigens, Viral(immunology); Blood Donors; CD4-Positive T-Lymphocytes(immunology; transplantation); CD8-Positive T-Lymphocytes(immunology; transplantation); Cell Culture Techniques(methods); Cytomegalovirus(immunology); Hematopoietic Stem Cell Transplantation(methods); Humans; Lymphocyte Activation; Peptides(immunology); Transplantation, Homologous
Curation Last Updated:2015-01-27 21:49:31