title: Analysis of the cross-talk of Epstein-Barr virus-infected B cells with T cells in the marmoset.
abstract: Despite the well-known association of Epstein-Barr virus (EBV), a lymphocryptovirus (LCV), with multiple sclerosis, a clear pathogenic role for disease progression has not been established. The translationally relevant experimental autoimmune encephalomyelitis (EAE) model in marmoset monkeys revealed that LCV-infected B cells have a central pathogenic role in the activation of T cells that drive EAE progression. We hypothesized that LCV-infected B cells induce T-cell functions relevant for EAE progression. In the current study, we examined theex vivocross-talk between lymph node mononuclear cells (MNCs) from EAE marmosets and (semi-) autologous EBV-infected B-lymphoblastoid cell lines (B-LCLs). Results presented here demonstrate that infection with EBV B95-8 has a strong impact on gene expression profile of marmoset B cells, particularly those involved with antigen processing and presentation or co-stimulation to T cells. At the cellular level, we observed that MNC co-culture with B-LCLs induced decrease of CCR7 expression on T cells from EAE responder marmosets, but not in EAE monkeys without clinically evident disease. B-LCL interaction with T cells also resulted in significant loss of CD27 expression and reduced expression of IL-23R and CCR6, which coincided with enhanced IL-17A production. These results highlight the profound impact that EBV-infected B-LCL cells can have on second and third co-stimulatory signals involved in (autoreactive) T-cell activation.
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands; Department of Neuroscience, University Groningen, University Medical Center, Groningen, The Netherlands.
authors.forename: Jordon
authors.initials: J
authors.lastname: Dunham
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre , Rijswijk, The Netherlands.
authors.forename: Nikki
authors.initials: N
authors.lastname: van Driel
authors.affiliation: Department of Neuroscience, University Groningen, University Medical Center , Groningen, The Netherlands.
authors.forename: Bart Jl
authors.initials: BJ
authors.lastname: Eggen
authors.affiliation: Department of Neuroscience, University Groningen, University Medical Center , Groningen, The Netherlands.
authors.forename: Chaitali
authors.initials: C
authors.lastname: Paul
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands; Department of Neuroscience, University Groningen, University Medical Center, Groningen, The Netherlands.
authors.forename: Bert A
authors.initials: BA
authors.lastname: 't Hart
authors.affiliation: Department of Neuroscience, University Groningen, University Medical Center , Groningen, The Netherlands.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre , Rijswijk, The Netherlands.
authors.forename: Yolanda S
authors.initials: YS
authors.lastname: Kap