Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome: a preliminary study

Biol Psychiatry. 2007 Feb 1;61(3):273-8. doi: 10.1016/j.biopsych.2006.06.012. Epub 2006 Sep 25.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Autoantigens / analysis
  • Autoantigens / immunology
  • Blood Cell Count
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology
  • Child
  • Data Interpretation, Statistical
  • Female
  • Flow Cytometry
  • Humans
  • Immune Tolerance / physiology*
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lectins, C-Type
  • Lymphocyte Count
  • Male
  • Streptococcal Infections / immunology
  • T-Lymphocytes / physiology*
  • Tic Disorders / immunology
  • Tourette Syndrome / immunology*
  • Tourette Syndrome / psychology

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Autoantigens
  • CD69 antigen
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type