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

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 cell...

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Main Authors: Olga Antsiferova, Anne Müller, Patrick C Rämer, Obinna Chijioke, Bithi Chatterjee, Ana Raykova, Raquel Planas, Mireia Sospedra, Anatoliy Shumilov, Ming-Han Tsai, Henri-Jacques Delecluse, Christian Münz
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-08-01
Series:PLoS Pathogens
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25165855/?tool=EBI
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author Olga Antsiferova
Anne Müller
Patrick C Rämer
Obinna Chijioke
Bithi Chatterjee
Ana Raykova
Raquel Planas
Mireia Sospedra
Anatoliy Shumilov
Ming-Han Tsai
Henri-Jacques Delecluse
Christian Münz
author_facet Olga Antsiferova
Anne Müller
Patrick C Rämer
Obinna Chijioke
Bithi Chatterjee
Ana Raykova
Raquel Planas
Mireia Sospedra
Anatoliy Shumilov
Ming-Han Tsai
Henri-Jacques Delecluse
Christian Münz
author_sort Olga Antsiferova
collection DOAJ
description 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.
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spelling doaj.art-e25caa9499d24c2d95619727227fe2222022-12-21T16:58:12ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-08-01108e100433310.1371/journal.ppat.1004333Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice.Olga AntsiferovaAnne MüllerPatrick C RämerObinna ChijiokeBithi ChatterjeeAna RaykovaRaquel PlanasMireia SospedraAnatoliy ShumilovMing-Han TsaiHenri-Jacques DelecluseChristian MünzEpstein 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25165855/?tool=EBI
spellingShingle Olga Antsiferova
Anne Müller
Patrick C Rämer
Obinna Chijioke
Bithi Chatterjee
Ana Raykova
Raquel Planas
Mireia Sospedra
Anatoliy Shumilov
Ming-Han Tsai
Henri-Jacques Delecluse
Christian Münz
Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice.
PLoS Pathogens
title Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice.
title_full Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice.
title_fullStr Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice.
title_full_unstemmed Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice.
title_short Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice.
title_sort adoptive transfer of ebv specific cd8 t cell clones can transiently control ebv infection in humanized mice
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25165855/?tool=EBI
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