title: Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome: a preliminary study.
abstract: BACKGROUND
  Post-streptococcal autoimmune inflammation of basal ganglia was suggested to be an etiological factor in some cases of Tourette syndrome (TS). Since regulatory T (T reg) cells play a major role in preventing autoimmunity, we hypothesized that a defect in T reg cells may be present in children with TS. We also postulated that group A beta hemolytic streptococcal infections could promote autoimmune responses by releasing exotoxins (streptococcal pyrogenic exotoxins [SPE]).
  
  
  METHODS
  We analyzed peripheral blood of TS patients and healthy age-matched control subjects by fluorescence-activated cell sorting (FACS) on multiple occasions and determined the numbers of CD4(+)CD25(+)CD69(-) T reg cells. Further, we quantified the number of CD4(+) and CD8(+) lymphocytes with regard to Vbeta chains to which SPEs are known to bind.
  
  
  RESULTS
  A significant decrease in T reg cells was observed in patients with moderate to severe TS symptoms compared with healthy age-matched control children. A decrease in T reg cell number was also noted during symptom exacerbations in five out of six patients. Further, we found a significant decrease in numbers of CD8(+)Vbeta18(+) T cells in moderate to severe TS patients.
  
  
  CONCLUSIONS
  These data support our hypothesis that at least some TS patients may have a decreased capacity to inhibit autoreactive lymphocytes through a deficit in T reg cells. Interactions of host T cell immunity and microbial factors may also contribute to the pathogenesis of TS.
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut 06520, USA. ivana.kawikova@yale.edu
authors.forename: Ivana
authors.initials: I
authors.lastname: Kawikova
authors.forename: James F
authors.initials: JF
authors.lastname: Leckman
authors.forename: Holger
authors.initials: H
authors.lastname: Kronig
authors.forename: Lily
authors.initials: L
authors.lastname: Katsovich
authors.forename: Debra E
authors.initials: DE
authors.lastname: Bessen
authors.forename: Musie
authors.initials: M
authors.lastname: Ghebremichael
authors.forename: Alfred L M
authors.initials: AL
authors.lastname: Bothwell
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000032:analysis / Q000276:immunology; D001772:Blood Cell Count; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D003627:Data Interpretation, Statistical; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D018655:Lymphocyte Count; D008297:Male; D013290:Streptococcal Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D013981:Tic Disorders / Q000276:immunology; D005879:Tourette Syndrome / Q000276:immunology* / Q000523:psychology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001324:Autoantigens; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D000099192:CD69 Antigens