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慢性鼻-鼻窦炎黏膜中的CD4和CD8调节性T细胞。

CD4 and CD8 regulatory T cells in chronic rhinosinusitis mucosa.

作者信息

Pant Harshita, Hughes Amy, Schembri Mark, Miljkovic Dijana, Krumbiegel Doreen

机构信息

Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide, Adelaide, South Australia, Australia.

出版信息

Am J Rhinol Allergy. 2014 Mar 1;28(2):83-89. doi: 10.2500/ajra.2013.28.4014.

Abstract

BACKGROUND

Chronic rhinosinusitis (CRS) mucosal inflammation is characterized by an accumulation of effector-memory T cells, but their immune regulatory potential has not been adequately examined. Coexpression of transcription factor, forkhead box P3 (Foxp3), and interleukin-2 receptor, CD25, in CD4+ and CD8+ T cells is linked with regulatory function in humans. The aim of this study was to investigate the regulatory T cell (Treg) phenotype of CD4+ (CD4Treg) and CD8+ (CD8Treg) T cells in peripheral blood (PB) and sinus mucosa of CRS patients.

METHODS

Prospective study was performed involving 32 CRS with nasal polyp (CRSwNP), 14 CRS without nasal polyp (CRSsNP), and 8 control patients. Sinus and PB T lymphocytes were stained with CD3, CD4, CD8, CD25, and Foxp3 and analyzed using flow cytometry. Relevant clinical characteristics, sinus bacterial culture results, and eosinophilic mucus were examined.

RESULTS

Sinus mucosa had a higher percentage of CD4Treg (CD3+CD4+CD25+Foxp3+) population compared with PB in all patients. The percentage of PB CD4Treg and CD8Treg (CD3+CD8+CD25+Foxp3+) was not significantly different between the study groups. CRS mucosal tissue had a higher percentage of CD4Treg and activated T-helper cells than controls. There was no significant difference in PB and mucosal CD4Treg populations in CRS patients based on the presence of allergy, sinus culture results, or eosinophilic mucus. In controls, increased mucosal CD4Treg correlated with coexisting allergy. Although overall CD4Treg numbers were higher, the regulatory potential of activated CD4+ T cells (CD4Treg/activated T-helper cell ratio) was significantly lower in CRS mucosa compared with controls. The CD8Treg subset was also significantly reduced in CRSwNP mucosa compared with controls.

CONCLUSION

A higher percentage of CD4Treg and activated T-helper cells in CRS mucosa suggests increased inflammation in CRS, independent of the presence of allergy, microbial culture results, or eosinophilic mucus. However, the decreased ratio of CD4Treg versus activated T-helper cells in CRS and reduced CD8Treg population in CRSwNPs indicates an inflammatory bias and the inability to control mucosal disease.

摘要

背景

慢性鼻-鼻窦炎(CRS)黏膜炎症的特征是效应记忆T细胞的积累,但其免疫调节潜能尚未得到充分研究。转录因子叉头框P3(Foxp3)和白细胞介素-2受体CD25在CD4⁺和CD8⁺T细胞中的共表达与人类的调节功能相关。本研究的目的是调查CRS患者外周血(PB)和鼻窦黏膜中CD4⁺(CD4Treg)和CD8⁺(CD8Treg)T细胞的调节性T细胞(Treg)表型。

方法

进行了一项前瞻性研究,纳入32例伴鼻息肉的CRS(CRSwNP)患者、14例不伴鼻息肉的CRS(CRSsNP)患者和8例对照患者。用CD3、CD4、CD8、CD25和Foxp3对鼻窦和PB T淋巴细胞进行染色,并使用流式细胞术进行分析。检查相关临床特征、鼻窦细菌培养结果和嗜酸性黏液。

结果

在所有患者中,鼻窦黏膜中CD4Treg(CD3⁺CD4⁺CD25⁺Foxp3⁺)群体的百分比高于PB。研究组之间PB CD4Treg和CD8Treg(CD3⁺CD8⁺CD25⁺Foxp3⁺)的百分比无显著差异。CRS黏膜组织中CD4Treg和活化辅助性T细胞的百分比高于对照组。基于是否存在过敏、鼻窦培养结果或嗜酸性黏液,CRS患者的PB和黏膜CD4Treg群体无显著差异。在对照组中,黏膜CD4Treg增加与并存的过敏相关。尽管总体CD4Treg数量较高,但与对照组相比,CRS黏膜中活化CD4⁺T细胞的调节潜能(CD4Treg/活化辅助性T细胞比率)显著降低。与对照组相比,CRSwNP黏膜中的CD8Treg亚群也显著减少。

结论

CRS黏膜中较高百分比的CD4Treg和活化辅助性T细胞表明CRS炎症增加,与是否存在过敏、微生物培养结果或嗜酸性黏液无关。然而,CRS中CD4Treg与活化辅助性T细胞的比率降低以及CRSwNP中CD8Treg群体减少表明存在炎症偏向且无法控制黏膜疾病。

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