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CD4+ FOXP3+ Regulatory T Cells Exhibit Impaired Ability to Suppress Effector T Cell Proliferation in Patients with Turner Syndrome.


ABSTRACT:

Objective

We investigated whether the frequency, phenotype, and suppressive function of CD4+ FOXP3+ regulatory T cells (Tregs) are altered in young TS patients with the 45,X karyotype compared to age-matched controls.

Design and methods

Peripheral blood mononuclear cells from young TS patients (n = 24, 17.4-35.9 years) and healthy controls (n = 16) were stained with various Treg markers to characterize their phenotypes. Based on the presence of thyroid autoimmunity, patients were categorized into TS (-) (n = 7) and TS (+) (n = 17). Tregs sorted for CD4+ CD25bright were co-cultured with autologous CD4+ CD25- target cells in the presence of anti-CD3 and -CD28 antibodies to assess their suppressive function.

Results

Despite a lower frequency of CD4+ T cells in the TS (-) and TS (+) patients (mean 30.8% and 31.7%, vs. 41.2%; P = 0.003 and P < 0.001, respectively), both groups exhibited a higher frequency of FOXP3+ Tregs among CD4+ T cells compared with controls (means 1.99% and 2.05%, vs. 1.33%; P = 0.029 and P = 0.004, respectively). There were no differences in the expression of CTLA-4 and the frequency of Tregs expressing CXCR3+, and CCR4+ CCR6+ among the three groups. However, the ability of Tregs to suppress the in vitro proliferation of autologous CD4+ CD25- T cells was significantly impaired in the TS (-) and TS (+) patients compared to controls (P = 0.003 and P = 0.041). Meanwhile, both the TS (-) and TS (+) groups had lower frequencies of naïve cells (P = 0.001 for both) but higher frequencies of effector memory cells (P = 0.004 and P = 0.002) than did the healthy control group.

Conclusions

The Tregs of the TS patients could not efficiently suppress the proliferation of autologous effector T cells, despite their increased frequency in peripheral CD4+ T cells.

SUBMITTER: Lee YA 

PROVIDER: S-EPMC4692523 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

CD4+ FOXP3+ Regulatory T Cells Exhibit Impaired Ability to Suppress Effector T Cell Proliferation in Patients with Turner Syndrome.

Lee Young Ah YA   Kim Hang-Rae HR   Lee Jeong Seon JS   Jung Hae Woon HW   Kim Hwa Young HY   Lee Gyung Min GM   Lee Jieun J   Sim Ji Hyun JH   Oh Sae Jin SJ   Chung Doo Hyun DH   Shin Choong Ho CH   Yang Sei Won SW  

PloS one 20151228 12


<h4>Objective</h4>We investigated whether the frequency, phenotype, and suppressive function of CD4+ FOXP3+ regulatory T cells (Tregs) are altered in young TS patients with the 45,X karyotype compared to age-matched controls.<h4>Design and methods</h4>Peripheral blood mononuclear cells from young TS patients (n = 24, 17.4-35.9 years) and healthy controls (n = 16) were stained with various Treg markers to characterize their phenotypes. Based on the presence of thyroid autoimmunity, patients were  ...[more]

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