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T cells specific for different latent and lytic viral proteins efficiently control epstein-barr virus-transformed B cells

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dc.contributor Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades
dc.contributor.author Nowakowska, Justyna
dc.contributor.author Stuehler, Claudia
dc.contributor.author Egli, Adrian
dc.contributor.author Battegay, Manuel
dc.contributor.author Rauser, Georg
dc.contributor.author Bantug, Glenn Robert
dc.contributor.author Brander, Christian
dc.contributor.author Hess, Christoph
dc.contributor.author Khanna, Nina
dc.date.accessioned 2015-11-09T08:59:03Z
dc.date.available 2015-11-09T08:59:03Z
dc.date.created 2015
dc.date.issued 2015
dc.identifier.citation Nowakowska, J., Stuehler, C., Egli, A., Battegay, M., Rauser, G., Bantug, G. R., et al. (2015). T cells specific for different latent and lytic viral proteins efficiently control epstein-barr virus-transformed B cells. Cytotherapy, 17(9), 1280-1291. ca_ES
dc.identifier.issn 1465-3249
dc.identifier.uri http://hdl.handle.net/10854/4339
dc.description.abstract Background aims. Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) belong to the most dreaded complications of immunosuppression. The efficacy of EBV-specific T-cell transfer for PTLD has been previously shown, yet the optimal choice of EBV-derived antigens inducing polyclonal CD4þ and CD8þ T cells that cover a wide range of human leukocyte antigen types and efficiently control PTLD remains unclear. Methods. A pool of 125 T-cell epitopes from seven latent and nine lytic EBV-derived proteins (EBVmix) and peptide pools of EBNA1, EBNA3c, LMP2a and BZLF1 were used to determine T-cell frequencies and to isolate T cells through the use of the interferon (IFN)-g cytokine capture system. We further evaluated the phenotype and functionality of the generated T-cell lines in vitro. Results. EBVmix induced significantly higher T-cell frequencies and allowed selecting more CD4þIFN-gþ and CD8þIFN-gþ cells than single peptide pools. T cells of all specificities expanded similarly in vitro, recognized cognate antigen, and, to a lower extent, EBV-infected cells, exerted moderate cytotoxicity and showed reduced alloreactivity. However, EBVmix-specific cells most efficiently controlled EBV-infected lymphoblastoid cell lines (LCLs). This control was mainly mediated by EBVspecific CD8þ cells with an oligoclonal epitope signature covering both latent and lytic viral proteins. Notably, EBVspecific CD4þ cells unable to control LCLs produced significantly less perforin and granzyme B, probably because of limited LCL epitope presentation. Conclusions. EBVmix induces a broader T-cell response, probably because of its coverage of latent and lytic EBV-derived proteins that may be important to control EBV-transformed B cells and might offer an improvement of T-cell therapies. ca_ES
dc.format application/pdf
dc.format.extent 12 p. ca_ES
dc.language.iso eng ca_ES
dc.publisher International Society for Cellular Therapy ca_ES
dc.rights Tots els drets reservats ca_ES
dc.rights (c) Elsevier
dc.subject.other Virus ca_ES
dc.subject.other Immunoteràpia ca_ES
dc.title T cells specific for different latent and lytic viral proteins efficiently control epstein-barr virus-transformed B cells ca_ES
dc.type info:eu-repo/semantics/article ca_ES
dc.identifier.doi https://doi.org/10.1016/j.jcyt.2015.06.003
dc.rights.accesRights info:eu-repo/semantics/closedAccess ca_ES
dc.type.version info:eu-repo/publishedVersion ca_ES
dc.indexacio Indexat a WOS/JCR ca_ES
dc.indexacio Indexat a SCOPUS

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