Chandelier
Senior Member (Voting Rights)
CD4 + T cells reactive to Epstein-Barr virus late lytic antigens are enriched in individuals with multiple sclerosis
Here, Bjornevik et al. investigated the CD4+ T cell response to EBV in individuals with MS, finding that these cells primarily reacted against EBV viral particle components.
Moreover, these responses were reduced upon B cell depletion therapy, which has shown therapeutic benefit in MS.
Although future work will determine whether these CD4+T cells are pathogenic drivers of disease, these findings highlight the therapeutic potential of approaches aimed at EBV and EBV-specific immune responses. —Courtney Malo
EBV-specific CD4+ T cell responses were twofold higher in individuals with untreated MS compared with healthy controls, whereas responses to other herpesviruses remained similar.
Anti-CD20 therapy initiation in treatment-naïve participants reduced these responses, a finding validated in an independent cohort, and eliminated viral shedding in saliva.
Our results establish preferential CD4+ T cell reactivity to EBV late lytic antigens as a key feature of MS, providing a framework for developing EBV-targeted therapies, including vaccines and antivirals.
Web | DOI | Science Translational Medicine | Paywall
Bjornevik, Kjetil; Mahler, João Vitor; Bilodeau, Philippe A.; Rød, Brit Ellen; Romanow, Gabriela; Mikami, Takahisa; Anderson, Monique; Bobrowski-Khoury, Natasha; Zhu, Huimin; Nguyen, James; Sun, Ying; Matiello, Marcelo; Housman, David; Nourbakhsh, Bardia; Myhr, Kjell-Morten; Torkildsen, Øivind; Sollid, Ludvig M.; Levy, Michael; Drosu, Natalia
Editor’s summary
Epstein-Barr virus (EBV) has been nearly definitively linked to development of multiple sclerosis (MS); however, the exact roles of EBV itself and the immune response to it are only now being elucidated.Here, Bjornevik et al. investigated the CD4+ T cell response to EBV in individuals with MS, finding that these cells primarily reacted against EBV viral particle components.
Moreover, these responses were reduced upon B cell depletion therapy, which has shown therapeutic benefit in MS.
Although future work will determine whether these CD4+T cells are pathogenic drivers of disease, these findings highlight the therapeutic potential of approaches aimed at EBV and EBV-specific immune responses. —Courtney Malo
Abstract
Multiple sclerosis (MS) pathogenesis is linked to Epstein-Barr virus (EBV), but the underlying immune mechanisms remain unclear. Using an optimized T cell assay, we demonstrate that CD4+ T cells from individuals with MS predominantly target EBV viral particle components, specifically the late lytic capsid and glycoprotein antigens, rather than latent antigens. In contrast, the Epstein-Barr nuclear antigen 1 (EBNA1) primarily activated CD8+ T cells.EBV-specific CD4+ T cell responses were twofold higher in individuals with untreated MS compared with healthy controls, whereas responses to other herpesviruses remained similar.
Anti-CD20 therapy initiation in treatment-naïve participants reduced these responses, a finding validated in an independent cohort, and eliminated viral shedding in saliva.
Our results establish preferential CD4+ T cell reactivity to EBV late lytic antigens as a key feature of MS, providing a framework for developing EBV-targeted therapies, including vaccines and antivirals.
Web | DOI | Science Translational Medicine | Paywall
