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风湿性心脏病中链球菌M蛋白影响下CD4(+)CD25(+)调节性T细胞的功能与发育分析

Functional and Developmental Analysis of CD4(+)CD25(+) Regulatory T Cells under the Influence of Streptococcal M Protein in Rheumatic Heart Disease.

作者信息

Abdul-Auhaimena Nidhal, Al-Kaabi Zaman I L

机构信息

Department of Microbiology, Alnahrain College of Medicine, P.O. Box 12444, Baghdad, Iraq.

出版信息

Iran J Med Sci. 2011 Jun;36(2):122-7.

PMID:23359747
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3556756/
Abstract

The purpose of this study was to determine the role of streptococcal M protein in naturally-occurring CD4(+)CD25(+) regulatory T cells (nTregs) function and development in rheumatic heart disease in Iraqi patients. Streptococcus pyogenes was isolated for subsequent M protein extraction. Also, peripheral blood nTregs and CD4(+) T cells were isolated by using Magnetic Cell Separation System. Tissue culture for isolated cells was performed in the presence and absence of M protein. Cell count was performed, and tumor necrosis factor alpha (TNF-α) and interleukin-4 (IL-4) were determined in culture supernatant using ELISA system. There was a significant positive correlation (P<0.01) between the number of proliferated nTregs and CD4(+) T cells in the presence as well as the absence of streptococcal M protein. Moreover, there was a significant negative correlation between the mean number of nTregs and CD4(+) T cells in mixed culture system in the absence of M protein (r=-0.995). There was also a positive, but not significant (P>0.05), association (r=0.353) between the mean number of nTregs and CD4(+) T cells in the presence of M protein. The M protein stimulated CD4(+) T cells to produce IL-4 in very little amount (<4 pg/ml) in all samples. Compared to the production of IL4, TNF-α was produced in higher concentrations in the culture supernatants. The findings of the study indicate that streptococcal M protein has an important role in increasing the proliferation of D4(+)CD25(+)regulatory T cells and CD4(+) T cells. However, CD4(+)CD25(+) regulatory T cells have lower suppressive activity against CD4(+) T cells in the presence of M protein.

摘要

本研究的目的是确定链球菌M蛋白在伊拉克风湿性心脏病患者自然发生的CD4(+)CD25(+)调节性T细胞(nTregs)功能及发育中的作用。分离化脓性链球菌以进行后续的M蛋白提取。此外,使用磁性细胞分离系统分离外周血nTregs和CD4(+) T细胞。在有和没有M蛋白的情况下对分离的细胞进行组织培养。进行细胞计数,并使用ELISA系统测定培养上清液中的肿瘤坏死因子α(TNF-α)和白细胞介素-4(IL-4)。在有和没有链球菌M蛋白的情况下,增殖的nTregs数量与CD4(+) T细胞数量之间存在显著正相关(P<0.01)。此外,在没有M蛋白的混合培养系统中,nTregs和CD4(+) T细胞的平均数量之间存在显著负相关(r=-0.995)。在有M蛋白的情况下,nTregs和CD4(+) T细胞的平均数量之间也存在正相关,但不显著(P>0.05)(r=0.353)。M蛋白刺激所有样本中的CD4(+) T细胞产生极少量的IL-4(<4 pg/ml)。与IL-4的产生相比,培养上清液中TNF-α的产生浓度更高。该研究结果表明,链球菌M蛋白在增加D4(+)CD25(+)调节性T细胞和CD4(+) T细胞的增殖方面具有重要作用。然而,在有M蛋白的情况下,CD4(+)CD25(+)调节性T细胞对CD4(+) T细胞的抑制活性较低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0117/3556756/fcae2d440a15/IJMS-36-122-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0117/3556756/2db8d1753650/IJMS-36-122-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0117/3556756/fcae2d440a15/IJMS-36-122-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0117/3556756/2db8d1753650/IJMS-36-122-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0117/3556756/fcae2d440a15/IJMS-36-122-g002.jpg

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CD69+ CD4+ CD25- T cells, a new subset of regulatory T cells, suppress T cell proliferation through membrane-bound TGF-beta 1.CD69+ CD4+ CD25- T细胞是调节性T细胞的一个新亚群,通过膜结合型转化生长因子β1抑制T细胞增殖。
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