Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Nat Commun. 2017 Apr 21;8:15067. doi: 10.1038/ncomms15067.
Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro. Ex vivo TCR repertoire analysis shows that immunization induces oligoclonal expansion of Tfh cells. By contrast, the Tfr pool has a TCR repertoire that more closely resembles that of regulatory T (Treg) cells. Our data thus indicate that the GC Tfh and Tfr pools are generated from distinct TCR repertoires, with Tfh cells expressing antigen-responsive TCRs to promote antibody responses, and Tfr cells expressing potentially autoreactive TCRs to suppress autoimmunity.
免疫会导致生发中心（GC）的形成，其中包含滤泡辅助性 T 细胞（Tfh）和滤泡调节性 T 细胞（Tfr）。T 细胞受体（TCR）特异性是否决定了 Tfh 和 Tfr 细胞的功能差异尚不清楚。本研究表明，免疫后抗原特异性 T 细胞优先募集到 GC 成为 Tfh 细胞，而不是 Tfr 细胞。Tfh 细胞，而不是 Tfr 细胞，在体外用相同的免疫原再次刺激时也能有效地增殖。体外 TCR 库分析表明，免疫诱导 Tfh 细胞的寡克隆扩增。相比之下，Tfr 池的 TCR 库更类似于调节性 T（Treg）细胞。因此，我们的数据表明，GC 中的 Tfh 和 Tfr 池来自不同的 TCR 库，Tfh 细胞表达抗原反应性 TCR 以促进抗体反应，而 Tfr 细胞表达潜在的自身反应性 TCR 以抑制自身免疫。
