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


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.

SUBMITTER: Antsiferova O 

PROVIDER: S-EPMC4148450 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Antsiferova Olga O   Müller Anne A   Rämer Patrick C PC   Chijioke Obinna O   Chatterjee Bithi B   Raykova Ana A   Planas Raquel R   Sospedra Mireia M   Shumilov Anatoliy A   Tsai Ming-Han MH   Delecluse Henri-Jacques HJ   Münz Christian C  

PLoS pathogens 20140828 8


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  ...[more]

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