title: Paucity of natural killer and cytotoxic T cells in human neuromyelitis optica lesions.
abstract: Neuromyelitis optica is a severe inflammatory demyelinating disease of the central nervous system. Most patients with neuromyelitis optica have circulating immunoglobulin G (IgG) antibodies against the astrocytic water channel protein aquaporin-4 (AQP4), which are pathogenic. Anti-AQP4 IgG-mediated complement-dependent astrocyte toxicity is a key mechanism of central nervous system damage in neuromyelitis optica, but the role of natural killer and cytotoxic T cells is unknown. Our objective was to determine whether natural killer and cytotoxic T cells play a role in human neuromyelitis optica lesions. We immunostained four actively demyelinating lesions, obtained from patients with anti-AQP4 IgG positive neuromyelitis optica, for Granzyme B and Perforin. The inflammatory cells were perivascular neutrophils, eosinophils and macrophages, with only occasional Granzyme B+ or Perforin+ cells. Greater than 95% of inflamed vessels in each lesion had no surrounding Granzyme B+ or Perforin+ cells. Granzyme B+ or Perforin+ cells were abundant in human spleen (positive control). Although natural killer cells produce central nervous system damage in mice injected with anti-AQP4 IgG, our findings here indicate that natural killer-mediated and T cell-mediated cytotoxicity are probably not involved in central nervous system damage in human neuromyelitis optica.
authors.affiliation: Academic Neurosurgery Unit, St. George's, University of London, University of California, San Francisco, California, USA.
authors.forename: Samira
authors.initials: S
authors.lastname: Saadoun
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Bridges
authors.forename: A S
authors.initials: AS
authors.lastname: Verkman
authors.forename: Marios C
authors.initials: MC
authors.lastname: Papadopoulos
mesh_terms: D001921:Brain / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D009471:Neuromyelitis Optica / Q000276:immunology / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology*