Successful in vitro priming of EBV-specific CD8+ T cells endowed with strong cytotoxic function from T cells of EBV-seronegative children

P. Comoli, F. Ginevri, R. Maccario, C. Frasson, U. Valente, S. Basso, M. Labirio, G. C. Huang, E. Verrina, F. Baldanti, F. Perfumo, F. Locatelli

Research output: Contribution to journalArticle

Abstract

Epstein-Barr virus (EBV)-seronegative transplant recipients are at high risk of developing EBV-associated post-transplant lymphoproliferative disorder (PTLD), and would maximally benefit from an EBV-directed T-cell therapy for prevention or treatment of PTLD. So far, efforts to activate CD8+ EBV-specific cytotoxic T lymphocytes (CTL) endowed with high specific cytotoxicity from EBV-seronegative children have failed. We compared the CD8+ CTL priming efficiency of three different modified activation protocols, based on lymphoblastoid cell lines (LCL) stimulation potentially enhanced by either LCL presentation through dendritic cells, or selection of IFN-γ+ cultured cells, or culture in the presence of rhIL-12 and rhIL-7, according to the standard protocol for reactivation of EBV-specific CTL. We found that only specific LCL stimulation in the presence of rhIL-12 and rhIL-7 was able to reproducibly expand EBV-specific CD8+ CTL endowed with strong cytotoxic activity from truly EBV-seronegative children. The lines thus activated, which included specificities toward EBV latent and lytic proteins, showed high percentage CD8+ T cells, with

Original languageEnglish
Pages (from-to)2169-2176
Number of pages8
JournalAmerican Journal of Transplantation
Volume6
Issue number9
DOIs
Publication statusPublished - Sep 2006

Keywords

  • CD8+ T-cell priming
  • Cytotoxic T lymphocytes
  • Epstein-Barr virus
  • Pediatric transplantation
  • Post-transplant lymphoproliferative disorder

ASJC Scopus subject areas

  • Immunology

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