title: 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.
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
authors.forename: Olga
authors.initials: O
authors.lastname: Antsiferova
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Müller
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Rämer
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
authors.forename: Obinna
authors.initials: O
authors.lastname: Chijioke
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
authors.forename: Bithi
authors.initials: B
authors.lastname: Chatterjee
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
authors.forename: Ana
authors.initials: A
authors.lastname: Raykova
authors.affiliation: Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Raquel
authors.initials: R
authors.lastname: Planas
authors.affiliation: Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Mireia
authors.initials: M
authors.lastname: Sospedra
authors.affiliation: Division of Pathogenesis of Virus Associated Tumors, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Anatoliy
authors.initials: A
authors.lastname: Shumilov
authors.affiliation: Division of Pathogenesis of Virus Associated Tumors, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Ming-Han
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Division of Pathogenesis of Virus Associated Tumors, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Henri-Jacques
authors.initials: HJ
authors.lastname: Delecluse
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002472:Cell Transformation, Viral / Q000502:physiology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*