title: Disrupted balance of T cells under natalizumab treatment in multiple sclerosis.
abstract: OBJECTIVE
  To compare effects of natalizumab on inflammatory and regulatory T cells with regard to expression of α4-integrin (CD49d).
  
  
  METHODS
  Twenty-seven natalizumab-naive and 8 natalizumab-treated patients with multiple sclerosis (MS), 7 patients with neuromyelitis optica (NMO) or NMO spectrum disorder, and 8 healthy controls were included. The positive rate of CD49d was analyzed and compared among T helper 1 (Th1), T helper 17 (Th17), and regulatory T (Treg) cells (CD49d+Th1, CD49d+Th17, and CD49d+Treg, respectively).
  
  
  RESULTS
  Natalizumab treatment increased CD49d ratios, CD49d+Th1/CD49d+Treg, and CD49d+Th17/CD49d+Treg. This indicates larger reduction of the CD49d+ population in Treg cells than in Th1 or Th17 cells. The CD49d ratios of 2 patients who experienced exacerbation during natalizumab treatment were remarkably higher than those of the other natalizumab-treated patients. Natalizumab treatment increased the expression of TBX21, RORC, interferon (IFN)-γ, and interleukin (IL)-17A, and decreased the expression of FOXP3 in CD49d+ memory CD4 T cells. Natalizumab treatment also increased the amount of IFN-γ and IL-17A secreted by CD49d+ memory CD4 T cells.
  
  
  CONCLUSIONS
  The reduction rate of the CD49d+ population in Treg cells was larger than that in Th1 or Th17 cells. Although the large reduction in CD49d+ population is beneficial for MS, the proinflammatory state of residual CD49d+ cells might, in part, explain the presence of disease activity under natalizumab treatment.
authors.affiliation: Department of Immunology, National Institute of Neuroscience (K.K., M.N., W.S., Y.L., T.Y.), and Multiple Sclerosis Center (W.S., T.O., M.A., Y.L., T.Y.) and Department of Neurology (Y.L., M.M.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; and Department of Neurology (K.K., R.T.), Kyoto University Graduate School of Medicine, Japan.
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Immunology, National Institute of Neuroscience (K.K., M.N., W.S., Y.L., T.Y.), and Multiple Sclerosis Center (W.S., T.O., M.A., Y.L., T.Y.) and Department of Neurology (Y.L., M.M.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; and Department of Neurology (K.K., R.T.), Kyoto University Graduate School of Medicine, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Immunology, National Institute of Neuroscience (K.K., M.N., W.S., Y.L., T.Y.), and Multiple Sclerosis Center (W.S., T.O., M.A., Y.L., T.Y.) and Department of Neurology (Y.L., M.M.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; and Department of Neurology (K.K., R.T.), Kyoto University Graduate School of Medicine, Japan.
authors.forename: Wakiro
authors.initials: W
authors.lastname: Sato
authors.affiliation: Department of Immunology, National Institute of Neuroscience (K.K., M.N., W.S., Y.L., T.Y.), and Multiple Sclerosis Center (W.S., T.O., M.A., Y.L., T.Y.) and Department of Neurology (Y.L., M.M.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; and Department of Neurology (K.K., R.T.), Kyoto University Graduate School of Medicine, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Department of Immunology, National Institute of Neuroscience (K.K., M.N., W.S., Y.L., T.Y.), and Multiple Sclerosis Center (W.S., T.O., M.A., Y.L., T.Y.) and Department of Neurology (Y.L., M.M.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; and Department of Neurology (K.K., R.T.), Kyoto University Graduate School of Medicine, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Araki
authors.affiliation: Department of Immunology, National Institute of Neuroscience (K.K., M.N., W.S., Y.L., T.Y.), and Multiple Sclerosis Center (W.S., T.O., M.A., Y.L., T.Y.) and Department of Neurology (Y.L., M.M.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; and Department of Neurology (K.K., R.T.), Kyoto University Graduate School of Medicine, Japan.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Immunology, National Institute of Neuroscience (K.K., M.N., W.S., Y.L., T.Y.), and Multiple Sclerosis Center (W.S., T.O., M.A., Y.L., T.Y.) and Department of Neurology (Y.L., M.M.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; and Department of Neurology (K.K., R.T.), Kyoto University Graduate School of Medicine, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Immunology, National Institute of Neuroscience (K.K., M.N., W.S., Y.L., T.Y.), and Multiple Sclerosis Center (W.S., T.O., M.A., Y.L., T.Y.) and Department of Neurology (Y.L., M.M.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; and Department of Neurology (K.K., R.T.), Kyoto University Graduate School of Medicine, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Immunology, National Institute of Neuroscience (K.K., M.N., W.S., Y.L., T.Y.), and Multiple Sclerosis Center (W.S., T.O., M.A., Y.L., T.Y.) and Department of Neurology (Y.L., M.M.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; and Department of Neurology (K.K., R.T.), Kyoto University Graduate School of Medicine, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura