Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Otolaryngology-Head and Neck Surgery, Tianjin First Center Hospital, Tianjin, China.
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Allergy Clin Immunol. 2016 Feb;137(2):462-73. doi: 10.1016/j.jaci.2015.07.025. Epub 2015 Aug 30.
Locally produced IgE contributes to the initiation and development of eosinophilic inflammation in eosinophilic nasal polyps independent of systemic atopy. However, whether CXCR5(+)CD4(+) T follicular helper (TFH) cells are involved in local IgE production at mucosal sites remains unexplored.
We sought to explore the presence, phenotype, and function of CXCR5(+)CD4(+) TFH cells in eosinophilic nasal polyp tissues compared with noneosinophilic nasal polyp and control normal nasal tissues.
TFH cell-surface phenotypes and subsets and B-cell subsets in nasal tissues and peripheral blood were studied by means of flow cytometry. Immunohistochemistry was used to detect the tissue location of TFH cells. Sorted nasal TFH cells and CXCR5(-) T cells were cultured with autologous naive B cells purified from blood.
Nasal TFH cells expressed inducible costimulator, programmed cell death protein 1, and the transcription factor B-cell lymphoma 6 (Bcl-6) at an intermediate level when compared with bona fide TFH cells in tonsils and circulating TFH cells. Although counts of total TFH cells and IL-21(+), IFN-γ(+), and IL-17(+) TFH cells were increased in both eosinophilic and noneosinophilic nasal polyp tissues compared with those in normal nasal tissues, IL-4(+) TFH cell counts were only increased in eosinophilic polyp tissues. IL-4 and IL-21 were involved in polyp TFH cell-induced IgE production from naive B cells, and nasal IL-4(+) TFH cell counts correlated highly with local IgE levels in vivo. IL-4(+)Bcl-6(+)CD4(+) TFH cells were identified in ectopic lymphoid structures in eosinophilic nasal polyps. TFH cells also positively correlated with germinal center B cells and plasma cells in nasal tissues.
Nasal IL-4(+) TFH cells might be involved in local IgE production in eosinophilic nasal polyps.
局部产生的 IgE 有助于嗜酸性粒细胞性鼻息肉中嗜酸性粒细胞炎症的起始和发展，而与系统性过敏无关。然而，CXCR5(+)CD4(+)滤泡辅助性 T 细胞（TFH）细胞是否参与黏膜部位的局部 IgE 产生仍未得到探索。
我们旨在探讨与非嗜酸性鼻息肉和对照正常鼻组织相比，嗜酸性鼻息肉组织中 CXCR5(+)CD4(+)TFH 细胞的存在、表型和功能。
通过流式细胞术研究鼻组织和外周血中 TFH 细胞表面表型和亚群以及 B 细胞亚群。免疫组织化学用于检测 TFH 细胞的组织定位。用从血液中纯化的自体幼稚 B 细胞培养分选的鼻 TFH 细胞和 CXCR5(-)T 细胞。
与扁桃体和循环 TFH 细胞中的真正 TFH 细胞相比，鼻 TFH 细胞表达诱导共刺激分子、程序性细胞死亡蛋白 1 和转录因子 B 细胞淋巴瘤 6（Bcl-6）处于中等水平。尽管与正常鼻组织相比，嗜酸性和非嗜酸性鼻息肉组织中总 TFH 细胞和 IL-21(+)、IFN-γ(+)和 IL-17(+)TFH 细胞的计数增加，但仅在嗜酸性息肉组织中增加了 IL-4(+)TFH 细胞计数。IL-4 和 IL-21 参与了 TFH 细胞诱导幼稚 B 细胞产生 IgE，鼻 IL-4(+)TFH 细胞计数与体内局部 IgE 水平高度相关。在嗜酸性鼻息肉的异位淋巴样结构中鉴定出 IL-4(+)Bcl-6(+)CD4(+)TFH 细胞。TFH 细胞还与鼻组织中的生发中心 B 细胞和浆细胞呈正相关。
鼻 IL-4(+)TFH 细胞可能参与嗜酸性鼻息肉中的局部 IgE 产生。
