title: The VZV/IE63-specific T cell response prevents herpes zoster in fingolimod-treated patients.
abstract: OBJECTIVE
  To assess longitudinally the antiviral immune response of T cells from patients with multiple sclerosis (MS) treated with fingolimod (FTY) vs other disease-modifying treatments (DMTs).
  
  
  METHODS
  We assessed cellular immune responses specific to influenza virus (FLU), JC virus (JCV), and varicella-zoster virus (VZV) using quantification of interferon-γ secretion by enzyme-linked immunospot in patients with MS on FTY (n = 31), including 2 with herpes zoster (HZ), natalizumab (n = 11), and other DMTs (n = 11). We used viral lysates for FLU and VZV and a pool of peptides for FLU, JCV (VP-1), and VZV (IE63).
  
  
  RESULTS
  Besides an expected drop of T cells, we found that, proportionally to the number of CD3(+) T cells, only FTY-treated patients with MS exhibited an increased VZV/IE63-specific T cell response peaking 6 months into treatment, a response that returned to baseline after 12 and 24 months. Two FTY-treated patients developed an HZ 6 months into treatment, coinciding with an absent VZV/IE63-specific T cell response. However, cellular immune responses specific to VZV lysate, JCV, and FLU (lysate and pool of peptide epitopes) were similar between all 3 categories (FTY, natalizumab, and other DMTs) of study patients.
  
  
  CONCLUSIONS
  FTY-treated patients with MS exhibit an increased VZV/IE63-specific cellular immune response after 6 months of treatment. FTY-treated patients who develop an HZ are not able to mount such a response, suggesting that a T cell response directed against this viral protein may be key in preventing the occurrence of HZ.
authors.affiliation: Laboratory of Neuroimmunology, Center of Research in Neurosciences (A.M., G. Perriard, M.C., F.V., R.D.P.), and Service of Neurology (G. Perrotta, M.S., R.D.P.), Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Amandine
authors.initials: A
authors.lastname: Mathias
authors.affiliation: Laboratory of Neuroimmunology, Center of Research in Neurosciences (A.M., G. Perriard, M.C., F.V., R.D.P.), and Service of Neurology (G. Perrotta, M.S., R.D.P.), Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Perriard
authors.affiliation: Laboratory of Neuroimmunology, Center of Research in Neurosciences (A.M., G. Perriard, M.C., F.V., R.D.P.), and Service of Neurology (G. Perrotta, M.S., R.D.P.), Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Canales
authors.affiliation: Laboratory of Neuroimmunology, Center of Research in Neurosciences (A.M., G. Perriard, M.C., F.V., R.D.P.), and Service of Neurology (G. Perrotta, M.S., R.D.P.), Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Fanny
authors.initials: F
authors.lastname: Vuilleumier
authors.affiliation: Laboratory of Neuroimmunology, Center of Research in Neurosciences (A.M., G. Perriard, M.C., F.V., R.D.P.), and Service of Neurology (G. Perrotta, M.S., R.D.P.), Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Perrotta
authors.affiliation: Laboratory of Neuroimmunology, Center of Research in Neurosciences (A.M., G. Perriard, M.C., F.V., R.D.P.), and Service of Neurology (G. Perrotta, M.S., R.D.P.), Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Myriam
authors.initials: M
authors.lastname: Schluep
authors.affiliation: Laboratory of Neuroimmunology, Center of Research in Neurosciences (A.M., G. Perriard, M.C., F.V., R.D.P.), and Service of Neurology (G. Perrotta, M.S., R.D.P.), Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Renaud
authors.initials: R
authors.lastname: Du Pasquier