title: Specific central nervous system recruitment of HLA-G(+) regulatory T cells in multiple sclerosis.
abstract: OBJECTIVE
  We have recently described a novel population of natural regulatory T cells (T(reg)) that are characterized by the expression of HLA-G and may be found at sites of tissue inflammation (HLA-G(pos) T(reg)). Here we studied the role of these cells in multiple sclerosis (MS), a prototypic autoimmune inflammatory disorder of the central nervous system (CNS).
  
  
  METHODS
  Sixty-four patients with different types of MS, 9 patients with other neurological diseases, and 20 healthy donors were included in this study. Inflamed brain lesions from 5 additional untreated MS patients were examined. HLA-G(pos) T(reg) were analyzed in the cerebrospinal fluid (CSF) by flow cytometry and in inflammatory demyelinating lesions of MS brain specimens by immunohistochemistry. Functional capacity was accessed and transmigration was determined using an in vitro model of the human blood-brain barrier (BBB).
  
  
  RESULTS
  HLA-G(pos) T(reg) were found enriched in the inflamed CSF of MS patients and in inflammatory demyelinating lesions of MS brain specimens. HLA-G(pos) T(reg) showed a strong propensity to transmigrate across BBB, which was vigorously driven by inflammatory chemokines, and associated with a gain of suppressive capacity upon transmigration. CSF-derived HLA-G(pos) T(reg) of MS patients represented a population of activated central memory activated T cells with an upregulated expression of inflammatory chemokine receptors and exhibiting full suppressive capacity. Unlike natural FoxP3-expressing T(reg), HLA-G(pos) T(reg) derived from peripheral blood were functionally unimpaired in MS.
  
  
  CONCLUSIONS
  In MS, HLA-G(pos) T(reg) may serve to control potentially destructive immune responses directly at the sites of CNS inflammation and to counterbalance inflammation once specifically recruited to the CNS.
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Yu-Hwa
authors.initials: YH
authors.lastname: Huang
authors.forename: Alla L
authors.initials: AL
authors.lastname: Zozulya
authors.forename: Christian
authors.initials: C
authors.lastname: Weidenfeller
authors.forename: Imke
authors.initials: I
authors.lastname: Metz
authors.forename: Dorothea
authors.initials: D
authors.lastname: Buck
authors.forename: Klaus V
authors.initials: KV
authors.lastname: Toyka
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
mesh_terms: D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D002465:Cell Movement; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell; D019713:Receptors, CCR5; D018121:Receptors, Cytokine