Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Immunology, Harvard Medical School, Boston, MA, USA.
Nat Immunol. 2019 Oct;20(10):1360-1371. doi: 10.1038/s41590-019-0472-4. Epub 2019 Sep 2.
Follicular regulatory T (T) cells have specialized roles in modulating follicular helper T (T) cell activation of B cells. However, the precise role of T cells in controlling antibody responses to foreign antigens and autoantigens in vivo is still unclear due to a lack of specific tools. A T cell-deleter mouse was developed that selectively deletes T cells, facilitating temporal studies. T 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 cells also resulted in increased self-reactive immunoglobulin (Ig) G and IgE. The increased IgE levels led us to interrogate the role of T cells in house dust mite models. T cells were found to control T13 cell-induced IgE. In vivo, loss of T cells increased house-dust-mite-specific IgE and lung inflammation. Thus, T cells control IgG and IgE responses to vaccines, allergens and autoantigens, and exert critical immunoregulatory functions before GC formation.
滤泡调节性 T (T) 细胞在调节滤泡辅助性 T (T) 细胞激活 B 细胞方面具有特殊作用。然而，由于缺乏特异性工具，T 细胞在体内控制针对外来抗原和自身抗原的抗体反应的确切作用仍不清楚。一种 T 细胞缺失小鼠被开发出来，该小鼠可选择性地缺失 T 细胞，从而便于进行时间研究。研究发现 T 细胞调节早期，但不调节晚期生发中心 (GC) 对控制抗原特异性抗体和 B 细胞记忆的反应。T 细胞的缺失也导致了自身反应性免疫球蛋白 (Ig) G 和 IgE 的增加。增加的 IgE 水平促使我们研究 T 细胞在屋尘螨模型中的作用。研究发现 T 细胞控制 T13 细胞诱导的 IgE。在体内，T 细胞缺失会增加屋尘螨特异性 IgE 和肺部炎症。因此，T 细胞控制疫苗、过敏原和自身抗原的 IgG 和 IgE 反应，并在 GC 形成之前发挥关键的免疫调节功能。
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