Horiuchi Shu, Wu Hanchih, Liu Wen-Chun, Schmitt Nathalie, Provot Jonathan, Liu Yang, Bentebibel Salah-Eddine, Albrecht Randy A, Schotsaert Michael, Forst Christian V, Zhang Bin, Ueno Hideki
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA.
Sci Adv. 2021 Oct 8;7(41):eabj1249. doi: 10.1126/sciadv.abj1249.
Memory T follicular helper (T) cells play an essential role to induce secondary antibody response by providing help to memory and naïve B cells. Here, we show that the transcription factor Tox2 is vital for the maintenance of T cells in germinal centers (GCs) and the generation of memory T cells. High Tox2 expression was almost exclusive to GC T cells among human tonsillar and blood CD4 T cell subsets. Tox2 overexpression maintained the expression of T-associated genes in T cell receptor–stimulated human GC T cells and inhibited their spontaneous conversion into T1-like cells. Tox2-deficient mice displayed impaired secondary T cell expansion upon reimmunization with an antigen and upon secondary infection with a heterologous influenza virus. Collectively, our study shows that Tox2 is highly integrated into establishment of durable GC T cell responses and development of memory T cells in mice and humans.
记忆性滤泡辅助性T（Tfh）细胞通过为记忆性B细胞和初始B细胞提供帮助，在诱导二次抗体反应中发挥着至关重要的作用。在此，我们表明转录因子Tox2对于生发中心（GC）中Tfh细胞的维持以及记忆性T细胞的产生至关重要。在人类扁桃体和血液CD4 T细胞亚群中，高Tox2表达几乎仅见于GC Tfh细胞。Tox2过表达维持了T细胞受体刺激的人类GC Tfh细胞中Tfh相关基因的表达，并抑制了它们自发转化为T1样细胞。在用抗原再次免疫以及用异源流感病毒二次感染时，Tox2缺陷小鼠的二次T细胞扩增受损。总体而言，我们的研究表明Tox2高度整合于小鼠和人类中持久的GC Tfh细胞反应的建立以及记忆性T细胞的发育过程。
