Institute of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom.
PLoS One. 2012;7(11):e49715. doi: 10.1371/journal.pone.0049715. Epub 2012 Nov 16.
Th17 cells are pro-inflammatory CD4⁺T cells, which are important in immune responses against fungal pathogens and extracellular bacteria and have also been implicated in various autoimmune syndromes. However, their role in supporting B cell responses in these scenarios remains unclear, representing a significant lapse in our understanding of the role Th17 play in vaccine responses and the regulation of autoimmunity. We employed T cell and B cell receptor transgenic mice specific for model antigens, and adoptive transfer approaches that allowed the tracking of cognate B and T cells in situ and ex vivo using immunological methods. We have found that T cells activated under Th17 polarising conditions have a greater capacity to provide cognate B cell help compared with Th1 polarised populations, supporting higher expansion of antigen specific B cells and enhanced antibody titres. This advantage is associated with the increased persistence of Th17 polarised cells in areas of the lymph nodes where they can provide help (i.e. the B cell follicles). Also the Th17 cells are characterised by their higher expression of ICOS, a costimulatory molecule important for B cell help. Surprisingly, contrary to published reports, Th17 cells were not detected inside germinal centres, although they were found in close proximity to cognate B cells in the follicle early in the genesis of the humoral immune response. These data indicate that, Th17 cells have a more significant role earlier in the initiation/development of the germinal centre response and/or germinal centre-independent events, consistent with their early effector status.
Th17 细胞是促炎型 CD4+T 细胞,在针对真菌病原体和细胞外细菌的免疫反应中具有重要作用,并且还与各种自身免疫综合征有关。然而,它们在支持这些情况下 B 细胞反应中的作用仍不清楚,这代表了我们对 Th17 在疫苗反应和自身免疫调节中的作用的理解存在重大缺失。我们使用针对模型抗原的 T 细胞和 B 细胞受体转基因小鼠,以及采用过继转移方法,使用免疫学方法原位和体外追踪同源 B 和 T 细胞。我们发现,在 Th17 极化条件下激活的 T 细胞与 Th1 极化群体相比,具有更大的提供同源 B 细胞辅助的能力,支持抗原特异性 B 细胞的更高扩增和增强的抗体滴度。这种优势与 Th17 极化细胞在它们可以提供帮助的淋巴结区域(即 B 细胞滤泡)中的持久性增加有关。此外,Th17 细胞的特征还在于其高水平表达 ICOSL,这是一种对 B 细胞辅助很重要的共刺激分子。令人惊讶的是,与已发表的报告相反,Th17 细胞未在生发中心内检测到,尽管在体液免疫反应的早期,在滤泡中可以发现它们与同源 B 细胞紧密相邻。这些数据表明,Th17 细胞在生发中心反应和/或生发中心独立事件的起始/发展早期具有更重要的作用,这与其早期效应器状态一致。