克罗恩病中的CD4+CD25+CD127低表达FoxP3+调节性T细胞

CD4+CD25+CD127low FoxP3+ regulatory T cells in Crohn's disease.

作者信息

Khalili Ali, Ebrahimpour Soheil, Maleki Iradj, Abediankenari Saeid, Afrouzi Mousa Mohammadnia

机构信息

Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, I.R. Iran.

Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, I.R. Iran.

出版信息

Rom J Intern Med. 2018 Sep 1;56(3):158-166. doi: 10.2478/rjim-2018-0006.

DOI:10.2478/rjim-2018-0006

PMID:29453928

Abstract

BACKGROUND

Regulatory T (Treg) cell plays a key role in autoimmune diseases. We evaluated the regulatory function and frequency of Treg cells and secreted IL-10, IL-35 concentration in Crohn's disease (CD).

METHODS

Twenty-three patients with CD and 25 healthy controls (HC) were included in this study. We analysed the alteration of Tregs frequency using flow cytometry for CD4, CD25, CD127 and FoxP3 markers. Surface expression of CD4, CD25 and CD127 markers were used for isolation of relatively pure Treg cells. Suppressive activity of Tregs was determined by measuring their ability to inhibit the proliferation of T responder (Tres) cells. In addition, the amounts of IL-10 and IL-35 cytokines in co-culture supernatants were measured by ELISA assay after stimulation with anti-CD2/CD3/CD28.

RESULTS

CD patients had significantly lower frequency of CD4+ CD25+ CD127low FoxP3+ Treg cells in comparison with controls (2.17 ± 1.04 vs. 2.83 ± 1.07, p = 0.0352). Additionally, Treg cells mediated suppression was not significantly different in CD patients compared to controls. There was a significant difference in IL-10 secretion in response to anti-CD2/CD3/CD28 stimulation compared with HC (p = 0.0074).

CONCLUSION

The frequency of CD4+ CD25+ CD127low FoxP3+ Tregs decreased in active stage of CD but there was no impaired suppressive function of CD4+ CD25+ CD127low FoxP3+ Treg cells. We suggest that an alteration in the balance of Tregs and T effectors may contribute to pathogenesis of CD.

摘要

背景

调节性T（Treg）细胞在自身免疫性疾病中起关键作用。我们评估了克罗恩病（CD）中Treg细胞的调节功能、频率以及分泌的白细胞介素-10（IL-10）、白细胞介素-35（IL-35）浓度。

方法

本研究纳入了23例CD患者和25名健康对照（HC）。我们使用流式细胞术分析CD4、CD25、CD127和FoxP3标志物，以分析Tregs频率的改变。CD4、CD25和CD127标志物的表面表达用于分离相对纯化的Treg细胞。通过测量Treg细胞抑制T应答（Tres）细胞增殖的能力来确定其抑制活性。此外，在用抗CD2/CD3/CD28刺激后，通过酶联免疫吸附测定（ELISA）法测量共培养上清液中IL-10和IL-35细胞因子的量。

结果

与对照组相比，CD患者中CD4 + CD25 + CD127low FoxP3 + Treg细胞的频率显著降低（2.17±1.04对2.83±1.07，p = 0.0352）。此外，与对照组相比，CD患者中Treg细胞介导的抑制作用无显著差异。与HC相比，抗CD2/CD3/CD28刺激后IL-10分泌存在显著差异（p = 0.0074）。