Increased CD8+ T Cell Response to Epstein-Barr Virus Lytic Antigens in the Active Phase of Multiple Sclerosis

• DOI: 10.1371/journal.ppat.1003220
• Publication Date: 2013-04-11T20:49:57Z
• Authors: Daniela F. Angelini; Barbara Serafini; Eleonora Piras; Martina Severa; Eliana M. Coccia; Barbara Rosicarelli; Serena Ruggieri; Claudio Gasperini; Fabio Buttari; Diego Centonze; Rosella Mechelli; Marco Salvetti; Giovanna Borsellino; Francesca Aloisi; Luca Battistini
• Keywords: Natalizumab; Lytic cycle

It has long been known that multiple sclerosis (MS) is associated with an increased Epstein-Barr virus (EBV) seroprevalence and high immune reactivity to EBV infectious mononucleosis increases MS risk. This evidence led postulate infection plays a role in etiopathogenesis, although the mechanisms are debated. study was designed assess prevalence magnitude of CD8+ T-cell responses latent (EBNA-3A, LMP-2A) lytic (BZLF-1, BMLF-1) antigens relapsing-remitting patients (n = 113) healthy donors (HD) 43) investigate whether EBV-specific T cell response correlates disease activity, as defined by clinical evaluation gadolinium-enhanced magnetic resonance imaging. Using HLA class I pentamers, antigen-specific were detected fewer untreated inactive than active HD while frequency cells specific for higher patients, respectively. In contrast, cytomegalovirus did not differ between irrespective phase. Marked differences observed treated interferon-β natalizumab, two licensed drugs MS. Longitudinal studies revealed expansion during but relapse-free, natalizumab-treated patients. Analysis post-mortem brain samples showed expression protein BZLF-1 interactions cytotoxic lytically infected plasma inflammatory white matter lesions meninges. We therefore propose inability control could set stage intracerebral viral reactivation relapse.