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Increased CD8+ T cell response to Epstein-Barr virus lytic antigens in the active phase of multiple sclerosis

Daniela F Angelini1, Barbara Serafini, Eleonora Piras

  • 1Neuroimmunology Unit, Fondazione Santa Lucia-I.R.C.C.S., Rome, Italy.

Plos Pathogens
|April 18, 2013
PubMed

Insights

Epstein-Barr virus (EBV) reactivation may trigger multiple sclerosis (MS) relapses. Controlling EBV infection is crucial for managing MS disease activity and preventing relapses.

Area of Science:

  • Immunology
  • Neuroscience
  • Virology

Background:

  • Multiple sclerosis (MS) is linked to increased Epstein-Barr virus (EBV) seroprevalence and immune reactivity.
  • Infectious mononucleosis, caused by EBV, is a known risk factor for MS.
  • The precise role and mechanisms of EBV in MS pathogenesis remain debated.

Purpose of the Study:

  • To assess CD8+ T-cell responses to EBV latent and lytic antigens in relapsing-remitting MS patients and healthy donors.
  • To investigate the correlation between EBV-specific CD8+ T-cell responses and MS disease activity.
  • To analyze EBV-specific T-cell responses in MS patients treated with interferon-β and natalizumab.

Main Methods:

  • Quantification of CD8+ T-cell responses to EBV latent (EBNA-3A, LMP-2A) and lytic (BZLF-1, BMLF-1) antigens using HLA class I pentamers.
  • Comparison of responses between MS patients (n=113) and healthy donors (n=43), stratified by disease activity and treatment.
  • Analysis of cytomegalovirus-specific CD8+ T-cell responses as a control.
  • Longitudinal assessment of T-cell responses during disease flares and remission.
  • Examination of post-mortem MS brain tissue for EBV protein expression and immune cell interactions.

Main Results:

  • CD8+ T-cell responses to EBV lytic antigens were lower in untreated inactive MS patients compared to active MS patients and healthy donors.
  • Frequencies of CD8+ T cells specific for EBV lytic and latent antigens were higher in active and inactive MS patients, respectively.
  • EBV-specific CD8+ T-cell responses differed significantly in patients treated with interferon-β and natalizumab.
  • Expansion of EBV lytic antigen-specific CD8+ T cells occurred during active disease in untreated MS patients.
  • EBV protein BZLF-1 expression and CD8+ T-cell interactions with infected plasma cells were observed in MS brain lesions.

Conclusions:

  • Inability to control EBV infection during inactive MS may predispose to intracerebral viral reactivation and disease relapse.
  • EBV reactivation is proposed as a potential trigger for MS relapses.
  • These findings highlight the critical role of EBV control in managing MS.

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