Geißler Katharina, Markwart Robby, Requardt Robert Pascal, Weigel Cynthia, Schubert Katja, Scherag André, Rubio Ignacio, Guntinas-Lichius Orlando
Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany.
Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
PLoS One. 2017 Sep 6;12(9):e0183214. doi: 10.1371/journal.pone.0183214. eCollection 2017.
The palatine tonsils, localized in the oropharynx, are easily accessible secondary lymphoid tissue in humans. Inflammation of the palatine tonsils, local and chronic in case of chronic tonsillitis (CT) or acute in the presence of a peritonsillar abscess (PTA), ranks among the most common diseases in otolaryngology. However, the functionality of tonsillar immune cells, notably T-cells, in the context of these immune pathologies is poorly understood. We have examined the functional status of human tonsillar T-cells in CT and compared it to the acute inflammatory setting of a PTA. Patients presenting with CT (n = 10) or unilateral PTA (n = 7) underwent bilateral tonsillectomy and a subgroup of 8 patients underwent additional blood sampling. T-cells were purified via automated magnetic selection and subjected to flow cytometry-based immunophenotyping. In addition, the response to T-cell receptor (TCR) stimulation was assessed at the level of proximal signaling, activation marker expression and proliferation. We observed no difference between the percentage of T helper (CD4(+)) cells from tonsil tissue in CT and PTA, but observed a trend towards a higher percentage of T helper cells in the blood of patients with PTA versus CT, probably reflecting an acute, systemic bacterial infection in the former cohort. Tonsils from CT harbored more PD-1(+) CD4(+) T-cells, pointing to T-cell exhaustion due to chronic infection. This notion was supported by functional studies that showed a tendency to weaker TCR responses of tonsillar T-cells from CT. Intriguingly, tonsillar T-cells recurrently featured a dampened response to T-cell receptor stimulation at the level of receptor proximal signaling steps compared to peripheral T-cells. In sum, our study documents distinct differences in tonsillar T-cell class distribution and function between the various pathological conditions. Our observations are consistent with the concept that tonsillar T-cells react to infections by eliciting specific immunological responses in chronic versus acute settings of inflammation.
腭扁桃体位于口咽,是人类易于触及的二级淋巴组织。腭扁桃体发炎,在慢性扁桃体炎(CT)时为局部性和慢性炎症,在存在扁桃体周脓肿(PTA)时为急性炎症,是耳鼻喉科最常见的疾病之一。然而,在这些免疫病理情况下,扁桃体免疫细胞尤其是T细胞的功能尚不清楚。我们研究了CT患者扁桃体T细胞的功能状态,并将其与PTA的急性炎症情况进行比较。患有CT(n = 10)或单侧PTA(n = 7)的患者接受了双侧扁桃体切除术,8名患者的亚组进行了额外的血液采样。通过自动磁性分选纯化T细胞,并进行基于流式细胞术的免疫表型分析。此外,在近端信号传导、激活标志物表达和增殖水平评估对T细胞受体(TCR)刺激的反应。我们观察到CT和PTA患者扁桃体组织中辅助性T细胞(CD4(+))的百分比没有差异,但观察到PTA患者血液中辅助性T细胞百分比高于CT患者的趋势,这可能反映了前一组患者存在急性全身性细菌感染。CT患者的扁桃体含有更多的PD-1(+) CD4(+) T细胞,表明由于慢性感染导致T细胞耗竭。功能研究支持了这一观点,该研究表明CT患者扁桃体T细胞的TCR反应倾向于较弱。有趣的是,与外周T细胞相比,扁桃体T细胞在受体近端信号传导步骤水平对T细胞受体刺激的反应反复出现减弱。总之,我们的研究记录了不同病理状况下扁桃体T细胞类别分布和功能的明显差异。我们的观察结果与扁桃体T细胞在慢性与急性炎症环境中通过引发特异性免疫反应来应对感染的概念一致。