Document Detail


Impairment of regulatory T-cell function in autoimmune thyroid disease.
MedLine Citation:
PMID:  23379353     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Abigail B Glick; Alaina Wodzinski; Pingfu Fu; Alan D Levine; David N Wald
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Thyroid : official journal of the American Thyroid Association     Volume:  23     ISSN:  1557-9077     ISO Abbreviation:  Thyroid     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-07-09     Completed Date:  2014-01-27     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  9104317     Medline TA:  Thyroid     Country:  United States    
Other Details:
Languages:  eng     Pagination:  871-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Autoimmune Diseases / genetics,  immunology*
Child
Coculture Techniques
Down Syndrome / complications,  immunology
Female
Graves Disease / complications,  immunology*
Hashimoto Disease / complications,  immunology*
Humans
Male
Middle Aged
T-Lymphocytes, Regulatory / immunology*,  physiology
Grant Support
ID/Acronym/Agency:
AI-083609/AI/NIAID NIH HHS; AT-006I536/AT/NCCAM NIH HHS; DK-054213/DK/NIDDK NIH HHS; HD057581-05/HD/NICHD NIH HHS; UL1 TR000439/TR/NCATS NIH HHS; UL1RR024989/RR/NCRR NIH HHS; UL1TR000439/TR/NCATS NIH HHS
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