Matsumiya Hiroshi, Kawata Koji, Kamekura Ryuta, Tsubomatsu Chieko, Jitsukawa Sumito, Asai Takamasa, Akasaka Syunsuke, Kamei Motonari, Yamashita Keiji, Ito Fumie, Kubo Terufumi, Sato Noriyuki, Takano Ken-Ichi, Himi Tetsuo, Ichimiya Shingo
Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Immunol Lett. 2017 Nov;191:23-30. doi: 10.1016/j.imlet.2017.07.012. Epub 2017 Jul 26.
Florid reactive follicular hyperplasia (FRFH), which is characterized by large germinal centers (GCs) within normal lymphoid follicles, is often observed in benign lesions of lymph nodes and other tissues. Because of the histologic similarity of FRFH to tumorous lesions such as follicular lymphoma, careful pathological examination is required to evaluate such lesions; however, little is known about the mechanism underlying the development of FRFH. In this study, we investigated T follicular helper (Tfh) cells in hyperplastic tonsils of patients with obstructive sleep apnea syndrome (OSA), which frequently exhibits typical FRFH. When we analyzed tonsils of OSA and recurrent tonsillitis (RT) as a control, tonsils of OSA were found to harbor Tfh cells with a nearly 3-fold higher ratio in total CD4 T cells than that in tonsils of RT. Further analysis showed that, in comparison to Tfh cells of RT tonsils, Tfh cells of OSA tonsils were relatively tolerant to CD3-mediated activation-induced cell death (AICD) and also expressed lower levels of a Bob1 transcription coactivator and IL-4, which fosters the development of GC-B cells. Given that Bob1 controls the proliferative activity in response to CD3 stimulation and has been suggested to have a role in the production of IL-4 in Tfh cells, the unique structure of FRFH is possibly associated with the function of Bob1 Tfh cells.
florid反应性滤泡增生（FRFH）的特征是正常淋巴滤泡内有大的生发中心（GCs），常见于淋巴结和其他组织的良性病变中。由于FRFH在组织学上与滤泡性淋巴瘤等肿瘤性病变相似，因此需要仔细的病理检查来评估此类病变；然而，对于FRFH发生发展的潜在机制知之甚少。在本研究中，我们调查了阻塞性睡眠呼吸暂停综合征（OSA）患者增生扁桃体中的T滤泡辅助（Tfh）细胞，OSA常表现出典型的FRFH。当我们将OSA患者的扁桃体与作为对照的复发性扁桃体炎（RT）患者的扁桃体进行分析时，发现OSA患者的扁桃体中Tfh细胞在总CD4 T细胞中的比例比RT患者扁桃体中的比例高近3倍。进一步分析表明，与RT扁桃体的Tfh细胞相比，OSA扁桃体的Tfh细胞对CD3介导的活化诱导细胞死亡（AICD）相对耐受，并且Bob1转录共激活因子和IL-4的表达水平也较低，而IL-4促进GC-B细胞的发育。鉴于Bob1控制对CD3刺激的增殖活性，并被认为在Tfh细胞中IL-4的产生中起作用，FRFH的独特结构可能与Bob1 Tfh细胞的功能有关。
