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PLoS Pathog. 2014 Aug 28;10(8):e1004333. doi: 10.1371/journal.ppat.1004333. eCollection 2014 Aug.

Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice.

Author information

1
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
2
Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zürich, Zürich, Switzerland.
3
Division of Pathogenesis of Virus Associated Tumors, German Cancer Research Centre (DKFZ), Heidelberg, Germany.

Abstract

Epstein Barr virus (EBV) infection expands CD8+ T cells specific for lytic antigens to high frequencies during symptomatic primary infection, and maintains these at significant numbers during persistence. Despite this, the protective function of these lytic EBV antigen-specific cytotoxic CD8+ T cells remains unclear. Here we demonstrate that lytic EBV replication does not significantly contribute to virus-induced B cell proliferation in vitro and in vivo in a mouse model with reconstituted human immune system components (huNSG mice). However, we report a trend to reduction of EBV-induced lymphoproliferation outside of lymphoid organs upon diminished lytic replication. Moreover, we could demonstrate that CD8+ T cells against the lytic EBV antigen BMLF1 can eliminate lytically replicating EBV-transformed B cells from lymphoblastoid cell lines (LCLs) and in vivo, thereby transiently controlling high viremia after adoptive transfer into EBV infected huNSG mice. These findings suggest a protective function for lytic EBV antigen-specific CD8+ T cells against EBV infection and against virus-associated tumors in extra-lymphoid organs. These specificities should be explored for EBV-specific vaccine development.

PMID:
25165855
PMCID:
PMC4148450
DOI:
10.1371/journal.ppat.1004333
[Indexed for MEDLINE]
Free PMC Article

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