Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses
Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses
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DOI：
10.1038/s41590-019-0472-4
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发表时间：
2019-10-01
影响因子：
30.5
通讯作者：
Sage, Peter T.
中科院分区：
文献类型：
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作者：
Clement, Rachel L.;Daccache, Joe;Sage, Peter T.
滤泡调节性T（T-FR）细胞在调节B细胞的滤泡辅助性T（T-FH）细胞活化中具有专门的作用。然而，由于缺乏特异性工具，T-FR细胞在体内控制对外来抗原和自身抗原的抗体应答中的确切作用仍不清楚。开发了一种T-FR细胞删除小鼠，其选择性地删除T-FR细胞，便于时间研究。发现T-FR细胞调节早期而非晚期的生发中心（GC）反应以控制抗原特异性抗体和B细胞记忆。T-FR细胞的缺失也导致自身反应性免疫球蛋白（IG）G和IgE增加。IgE水平的增加使我们询问T-FR细胞在屋尘螨模型中的作用。发现T-FR细胞控制T（FH）13细胞诱导的IgE。在体内，T-FR细胞的损失增加了屋尘螨特异性IgE和肺部炎症。因此，T-FR细胞控制对疫苗、过敏原和自身抗原的IgG和IgE应答，并在GC形成之前发挥关键的免疫调节功能。
Follicular regulatory T (T-FR) cells have specialized roles in modulating follicular helper T (T-FH) cell activation of B cells. However, the precise role of T-FR cells in controlling antibody responses to foreign antigens and autoantigens in vivo is still unclear due to a lack of specific tools. A T-FR cell-deleter mouse was developed that selectively deletes T-FR cells, facilitating temporal studies. T-FR cells were found to regulate early, but not late, germinal center (GC) responses to control antigen-specific antibody and B cell memory. Deletion of T-FR cells also resulted in increased self-reactive immunoglobulin (Ig) G and IgE. The increased IgE levels led us to interrogate the role of T-FR cells in house dust mite models. T-FR cells were found to control T(FH)13 cell-induced IgE. In vivo, loss of T-FR cells increased house-dust-mite-specific IgE and lung inflammation. Thus, T-FR cells control IgG and IgE responses to vaccines, allergens and autoantigens, and exert critical immunoregulatory functions before GC formation.