title: Impairment of regulatory T-cell function in autoimmune thyroid disease.
abstract: BACKGROUND
  Autoimmune thyroid disease (AITD) pathogenesis may result from a loss of immune tolerance to thyroid antigens. Regulatory T cells (Tregs) control immune responses, prevent excessive inflammation, and may be dysfunctional in AITD. We investigated the role of Tregs in Hashimoto's thyroiditis (HT) and Graves' disease (GD), complicated by Down syndrome (DS). Our goal was to identify differences in CD4(+)CD25(high) Treg function or number in patients with GD and HT, compared to healthy controls (HC).
  
  
  METHODS
  Treg number was assessed by flow cytometric analysis in samples from 20 AITD patients (seven GD, 13 HT), nine HC, and seven individuals with DS, a genetic disorder associated with multiple autoimmune disorders including AITD. Treg function was assessed by the inhibition of proliferation (radioactive thymidine incorporation into DNA) of blood-derived T effector (Teff) cells by Tregs in a coculture. Various methods of stimulation were contrasted. Cytokine levels were determined in conditioned media from the co-cultures.
  
  
  RESULTS
  No differences were found in the frequency of Tregs as a percentage of CD4(+) cells between AITD and HC. AITD Tregs were less capable of inhibiting the proliferation of Teff cells when compared to HC; however, the impairment was dependent on the type of stimulation used. DS patients without AITD exhibited normal Treg function. We observed few differences in cytokine production between HC and AITD patients.
  
  
  CONCLUSIONS
  Tregs from AITD patients are partly dysfunctional, possibly explaining their autoimmunity. Future work will elucidate the diagnostic potential and pathophysiology of Tregs in AITD.
authors: Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors: Abigail B
authors: AB
authors: Glick
authors: Alaina
authors: A
authors: Wodzinski
authors: Pingfu
authors: P
authors: Fu
authors: Alan D
authors: AD
authors: Levine
authors: David N
authors: DN
authors: Wald
mesh_terms: D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D002648:Child; D018920:Coculture Techniques; D004314:Down Syndrome / Q000150:complications / Q000276:immunology; D005260:Female; D006111:Graves Disease / Q000150:complications / Q000276:immunology*; D050031:Hashimoto Disease / Q000150:complications / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000502:physiology
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