Smith Sarah E, Schlosser Rodney J, Yawn James R, Mattos Jose L, Soler Zachary M, Mulligan Jennifer K
Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
Am J Rhinol Allergy. 2017 Nov 1;31(6):352-356. doi: 10.2500/ajra.2017.31.4474.
CD8+ T cells and natural killer (NK) cells are cytotoxic cells that use granzyme B (GrB) and perforin. Defective cytotoxic function is known to play a role in dysregulated immune response as seen in chronic sinusitis, also referred to as chronic rhinosinusitis (CRS). However, to our knowledge, in the United States, neither GrB or perforin expression has been reported in patients with CRS.
The aim of this study was to investigate sinonasal cytotoxic cells, their mediators, and cell-specific distribution of these mediators in patients with CRS with nasal polyp (CRSwNP) and in patients with CRS without nasal polyp (CRSsNP).
Blood and sinus tissue samples were taken from patients with CRSsNP (n = 8) and CRSwNP (n = 8) at the time of surgery. Control subjects (n = 8) underwent surgery for cerebrospinal fluid leak repair or to remove non-hormone-secreting pituitary tumors. The cells were analyzed via flow cytometry by using CD8 expression to identify cytotoxic T cells and CD56 expression to identify NK cells. Intracellular GrB and perforin expression were analyzed with flow cytometry.
We observed no significant differences in plasma or peripheral blood immune cell numbers or specific levels of GrB or perforin among the groups. In the sinonasal mucosa of the patients with CRSsNP and the patients with CRSwNP, there was a significant decrease in GrB and perforin levels (p < 0.05) despite similar or increased numbers of cytotoxic cells when compared with the controls. The overall decrease in GrB and perforin in the sinonasal mucosa of the patients with CRSsNP and the patients with CRSwNP was due to decreased T cell production. There was no difference in total NK cell count or expression of perforin or GrB among all the groups.
Total levels of sinonasal GrB and perforin were decreased in the sinonasal mucosa of both the patients with CRSwNP and the patients with CRSsNP compared with the controls, whereas sinonasal CD8+ T cells, (but not NK cells,), intracellular stores of GrB and perforin were reduced in the patients with CRSwNP compared with the controls.
CD8+ T细胞和自然杀伤（NK）细胞是利用颗粒酶B（GrB）和穿孔素的细胞毒性细胞。已知细胞毒性功能缺陷在慢性鼻窦炎（也称为慢性鼻-鼻窦炎，CRS）中失调的免疫反应中起作用。然而，据我们所知，在美国，尚未有关于CRS患者GrB或穿孔素表达情况的报道。
本研究旨在调查伴鼻息肉的CRS（CRSwNP）患者和不伴鼻息肉的CRS（CRSsNP）患者鼻窦中的细胞毒性细胞、其介质以及这些介质的细胞特异性分布。
在手术时从CRSsNP患者（n = 8）和CRSwNP患者（n = 8）采集血液和鼻窦组织样本。对照受试者（n = 8）接受脑脊液漏修补手术或切除非激素分泌性垂体瘤手术。通过流式细胞术使用CD8表达来鉴定细胞毒性T细胞，使用CD56表达来鉴定NK细胞，对细胞进行分析。用流式细胞术分析细胞内GrB和穿孔素的表达。
我们观察到各组之间血浆或外周血免疫细胞数量以及GrB或穿孔素的特定水平无显著差异。在CRSsNP患者和CRSwNP患者的鼻窦黏膜中，尽管与对照组相比细胞毒性细胞数量相似或增加，但GrB和穿孔素水平显著降低（p < 0.05）。CRSsNP患者和CRSwNP患者鼻窦黏膜中GrB和穿孔素总体下降是由于T细胞产生减少所致。所有组之间NK细胞总数或穿孔素或GrB的表达无差异。
与对照组相比，CRSwNP患者和CRSsNP患者鼻窦黏膜中鼻窦GrB和穿孔素的总水平均降低，而与对照组相比，CRSwNP患者鼻窦CD8+ T细胞（而非NK细胞）内GrB和穿孔素的储存减少。
