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非哮喘性慢性鼻-鼻窦炎伴鼻息肉患者中的超抗原相关 T2 CD4 T 细胞。

Superantigen-related T2 CD4 T cells in nonasthmatic chronic rhinosinusitis with nasal polyps.

机构信息

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.

Institute of Health Sciences, Gyeongsang National University, Jinju, Korea; Department of Otorhinolaryngology, Gyeongsang National University, Jinju, Korea.

出版信息

J Allergy Clin Immunol. 2020 May;145(5):1378-1388.e10. doi: 10.1016/j.jaci.2019.12.915. Epub 2020 Jan 25.

Abstract

BACKGROUND

Staphylococcus aureus enterotoxin (SAE) superantigens are detected in nasal polyps (NPs), and SAE-specific IgE predicts asthma comorbidity in patients with NPs. However, roles of SAE superantigens and superantigen-related T-cell responses remain to be elucidated in nonasthmatic patients.

OBJECTIVE

We investigated the presence of SAEs and SAE-related T-cell receptor (TCR) Vβ (TCRVβ) in nonasthmatic NPs, the phenotypes and functions of SAE-related T cells, and the clinical implication of SAE-related T-cell expansion.

METHODS

Sinonasal tissue samples were obtained from patients with nonasthmatic chronic rhinosinusitis (CRS) with NPs (CRSwNP), patients with CRS without NPs (CRSsNP), and control subjects. SAE genes were detected by PCR, and the TCRVβ distribution and T-cell phenotypes were examined by flow cytometry.

RESULTS

Various SAE genes were detected not only in NPs but also in sinonasal mucosa from patients with CRSsNP and from controls. The S aureus enterotoxin I (SEI) gene was detected in all NPs. The fraction of SEI-responsive TCRVβ (TCRVβ1 and Vβ5.1) CD4 T cells was significantly increased only in NPs and the ethmoidal mucosa of patients with CRSwNP, indicating superantigen-induced expansion. The expanded TCRVβ5.1 CD4 T cells expressed proliferation marker Ki-67 and the T2 transcription factor GATA3. Furthermore, TCRVβ5.1 CD4 T cells in NPs highly expressed T2 markers, including IL-17RB, thymic stromal lymphoprotein receptor, and chemoattractant receptor-homologous molecule expressed on T2 cells, with a potent T2 cytokine-producing ability. Moreover, the expansion of TCRVβ1 or Vβ5.1 CD4 T cells was associated with the Lund-Mackay computed tomography score, indicating disease extent.

CONCLUSION

In nonasthmatic patients with CRSwNP, superantigen-related expansion of CD4 T cells with T2 differentiation was associated with the disease extent.

摘要

背景

金黄色葡萄球菌肠毒素(SAE)超抗原存在于鼻息肉(NPs)中,SAE 特异性 IgE 可预测 NP 患者的哮喘合并症。然而,SAE 超抗原和超抗原相关 T 细胞反应在非哮喘患者中的作用仍有待阐明。

目的

我们研究了非哮喘性 NP 患者中 SAE 及其相关 T 细胞受体(TCR)Vβ(TCRVβ)的存在、SAE 相关 T 细胞的表型和功能,以及 SAE 相关 T 细胞扩增的临床意义。

方法

从非哮喘性慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)患者、非哮喘性慢性鼻-鼻窦炎无鼻息肉(CRSsNP)患者和对照者的鼻-鼻窦组织样本中检测 SAE 基因,通过流式细胞术检测 TCRVβ 分布和 T 细胞表型。

结果

不仅在 NP 中,而且在 CRSsNP 患者和对照者的鼻-鼻窦黏膜中均检测到各种 SAE 基因。所有 NP 中均检测到金黄色葡萄球菌肠毒素 I(SEI)基因。仅在 NP 和 CRSwNP 患者的筛窦黏膜中,SEI 反应性 TCRVβ(TCRVβ1 和 Vβ5.1)CD4 T 细胞的比例显著增加,表明存在超抗原诱导的扩增。扩增的 TCRVβ5.1 CD4 T 细胞表达增殖标志物 Ki-67 和 T2 转录因子 GATA3。此外,NP 中的 TCRVβ5.1 CD4 T 细胞高度表达 T2 标志物,包括白细胞介素-17RB、胸腺基质淋巴生成素受体和 T2 细胞表达的趋化因子受体同源物,具有强大的 T2 细胞因子产生能力。此外,TCRVβ1 或 Vβ5.1 CD4 T 细胞的扩增与 Lund-Mackay 计算机断层扫描评分相关,表明疾病程度。

结论

在非哮喘性 CRSwNP 患者中,与疾病程度相关的 CD4 T 细胞的超抗原相关扩增具有 T2 分化特征。

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