Simultaneous generation of cytomegalovirus-specific CD8+ and CD4+ T lymphocytes by use of dendritic cells comodified with pp65 mRNA and pp65 protein
2005 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, Vol. 192, no 11, 1912-20 p.Article in journal (Refereed) Published
Cytomegalovirus (CMV) disease remains a severe complication in patients who have undergone transplantation. Viremia can be prevented and treated by the adoptive transfer of donor-derived CMV-directed T cells. To ensure long-term protection against CMV disease, it is important to transfer CMV antigen-specific T cells that represent both the CD8+ and the CD4+ subsets. In the present study, we used as stimulators dendritic cells (DCs) that were electroporated with in vitro-transcribed 5'-capped polyadenylated messenger RNA (mRNA) that encoded the CMV pp65 protein (i.e., pp65 mRNA). These DCs could efficiently activate CMV-directed CD8+ T cells, as assayed by tetramer staining, interferon- gamma production, and cytolytic activity. We also used DCs that were pulsed with a recombinant pp65 protein to activate CMV-directed CD4+ T cells. When DCs were comodified with pp65 mRNA and pp65 protein, large numbers of CMV-directed CD8+ and CD4+ T cells were generated simultaneously. The approach outlined in the present study can be adapted for a clinical protocol that circumvents potential virus-related biohazards and is available to all patients independently of their human leukocyte antigen haplotype.
Place, publisher, year, edition, pages
2005. Vol. 192, no 11, 1912-20 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-92710DOI: 10.1086/497700PubMedID: 16267762OAI: oai:DiVA.org:uu-92710DiVA: diva2:165887