Premium
Ex Vivo Priming of Naïve T Cells Into EBV‐Specific Th1/Tc1 Effector Cells by Mature Autologous DC Loaded with Apoptotic/Necrotic LCL
Author(s) -
Popescu Iulia,
Macedo Camila,
Zeevi Adriana,
Nellis Joseph,
Patterson Kevin R.,
Logar Allison,
Rowe David,
Reyes Jorge,
Rao Abdul S.,
Storkus Walter J.,
Fung John J.,
Metes Diana
Publication year - 2003
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1046/j.1600-6135.2003.00252.x
Subject(s) - medicine , immunology , cd8 , elispot , epstein–barr virus , t cell , priming (agriculture) , cytotoxic t cell , immunotherapy , immune system , cancer research , biology , virus , in vitro , botany , biochemistry , germination
Posttransplant lymphoproliferative disorders (PTLDs) represent life‐threatening complications of bone marrow and solid organ transplantation (SOTx). These are B‐cell malignancies triggered by Epstein‐Barr Virus (EBV) infection in chronically immunosuppressed (IS) recipients. Immunosuppressed EBV seronegative (EBV − ) organ recipients are at highest risk of developing PTLD owing to the lack of anti‐EBV memory T cells to control subsequent EBV challenges. Our aim is to establish effective anti‐EBV T‐cell generation protocols for prevention or treatment of PTLD encountered in SOTx. We have used autologous dendritic cells (DCs) loaded with apoptotic/necrotic lymphoblastoid cell lines (LCLs) to evaluate the ability of such an approach to activate naïve T cells in vitro . In EBV − individuals, both CD8+ and CD4+ T‐cell responses were amplified by this approach, as detected by IFN‐γ ELISPOT and cytotoxicity assays. The CD8+ T cells were poly‐specific anti‐EBNA3 A, ‐LMP2 and ‐BMLF1, with uniform reversion to a CD45RO+/RA‐phenotype, decreased CD62L expression, and up‐regulation of the activation markers CD28 and CD69. Addition of rhIL‐12 improved anti‐viral T‐cell responses and reduced the functional differences observed between EBV + and EBV − responders. In conclusion, the DC/LCL method promotes cross‐presentation of EBV‐associated epitopes and may serve as an effective protocol for the adoptive immunotherapy of PTLD in EBV − SOTx patients .