CD8+ T cells with distinct cytokine-producing features and low cytotoxic activity in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps
CD8+ T cells with distinct cytokine-producing features and low cytotoxic activity in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps
复制标题
CD8(+) T 细胞在伴有鼻息肉的嗜酸性和非嗜酸性慢性鼻-鼻窦炎中具有独特的细胞因子产生特征和低细胞毒活性。
DOI：
10.1111/cea.12758
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发表时间：
2016-09-01
影响因子：
6.1
通讯作者：
Liu, Z.
中科院分区：
文献类型：
--
作者：
Ma, J.;Shi, L. -L.;Liu, Z.
背景：CD 8（+）T细胞是细胞免疫的重要效应细胞;目的探讨鼻息肉合并CRS患者外周血中CD 8（+）T细胞的增殖特性、细胞毒活性及其与炎症反应的关系。用流式细胞术、免疫组化和免疫荧光法研究了CD 8（+）T细胞中的叉头盒P3（FOXP 3）、穿孔素和颗粒酶B。采用实时荧光定量RT-PCR或ELISA方法检测CD 8（+）T细胞亚群相关趋化因子及其受体的表达。结果与对照组相比，CD 8（+）T细胞总数和细胞毒性T淋巴细胞（Tc）1（IFN-γ（+））、Tc 2（IL-4（+））和Tc 17（IL-17 A（+））细胞亚群的百分比降低，并且FOXP 3（+）CD 8（+）调节性T细胞的百分比降低，在嗜酸性和非嗜酸性息肉中均发现了Tc 1/Tc 17，嗜酸性和非嗜酸性息肉中分别存在Tc 2偏态和Tc 1/Tc 17主导反应。鼻内CD 8（+）T细胞产生的IFN-γ和IL-4水平与CD 4（+）T细胞相似，甚至更高。鼻黏膜中Tc 1、Tc 17和Tc 2（IL-4（+）和IL-5（+））细胞亚群百分比分别与中性粒细胞和嗜酸性粒细胞计数呈正相关。引人注目的是，与外周血中的对应物相比，鼻CD 8（+）T细胞中穿孔素和颗粒酶B的表达和细胞毒活性显著降低。CXCL 16，CCL 17和CCL 20的表达与Tc 1，Tc 2和Tc 17细胞亚群数量呈正相关，分别在sinonasal mucosal，acceptance and Clinical Relevance CD 8（+）T细胞具有较低的细胞毒活性，然而，他们是一个显着的和以前低估的来源，在息肉的炎性细胞因子的生产。不同的Tc细胞亚群优势可能有助于明显偏嗜酸性和非嗜酸性息肉中的粒细胞炎症。
Background CD8(+) T cells are important effectors of cell-mediated immunity; however, their contribution to the pathogenesis of CRS is unclear.Objective This study aimed to characterize the cytokine-producing features and cytotoxic activity of CD8(+) T cells, and their correlation with inflammation patterns in CRS with nasal polyps.Methods The expression of IFN-gamma, IL-4, IL-5, IL-17A, forkhead box P3 (FOXP3), perforin, and granzyme B in CD8(+) T cells was studied by means of flow cytometry, immunohistochemistry, and immunofluorescence. The expression of CD8(+) T-cell subset relevant chemokines and chemokine receptors was detected by means of real-time RT-PCR or ELISA. The cytotoxic activity of sorted CD8(+) T cells was defined by anti-CD3-redirected killing assay.Results Compared with controls, elevated percentages of total CD8(+) T cells and cytotoxic T lymphocyte (Tc) 1 (IFN-gamma(+)), Tc2 (IL-4(+)), and Tc17 (IL-17A(+)) cell subset, and decreased percentages of FOXP3(+)CD8(+) regulatory T cells, were found in both eosinophilic and non-eosinophilic polyps with a Tc2-skewed and Tc1/Tc17-dominated response in eosinophilic and non-eosinophilic polyps, respectively. Nasal CD8(+) T cells were found to produce similar or even higher levels of IFN-gamma and IL-4 compared with CD4(+) T cells. Tc1 and Tc17, and Tc2 (IL-4(+) and IL-5(+)) cell subset percentages positively correlated with neutrophil and eosinophil counts in sinonasal mucosa, respectively. Strikingly, the expression of perforin and granzyme B and cytotoxic activity were significantly reduced in nasal CD8(+) T cells compared with their counterparts in peripheral blood. The expression of CXCL16, CCL17, and CCL20 positively correlated with Tc1, Tc2, and Tc17 cell subset number in sinonasal mucosa, respectively.Conclusion and Clinical Relevance CD8(+) T cells have low cytotoxic activity; nevertheless, they are a significant and previously underappreciated source of inflammatory cytokine production in polyps. Different Tc cell subset domination may contribute to distinctly biased granulocyte inflammation in eosinophilic and non-eosinophilic polyps.