Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, 12203 Berlin, Germany; and.
J Immunol. 2019 Oct 1;203(7):1743-1752. doi: 10.4049/jimmunol.1900611. Epub 2019 Aug 23.
Disease activity of autoimmune disorders such as multiple sclerosis and its mouse model experimental autoimmune encephalomyelitis (EAE) is temporarily suppressed by pregnancy. However, whether disease amelioration is due to nonspecific immunomodulation or mediated by Ag-specific regulation of disease-causing conventional T cells (Tcon) and immunosuppressive regulatory T cells (Tregs) remains elusive. In the current study, we systematically analyzed changes of the TCRβ repertoire driven by EAE and pregnancy using TCR sequencing. We demonstrate that EAE, but not pregnancy, robustly increased TCR repertoire clonality in both peripheral Tcon and Treg. Notably, pregnancy was required for the expansion of Treg harboring the dominant EAE-associated TRBV13-2 chain and increased the frequency of EAE-associated clonotypes within the Treg compartment. Our findings indicate that pregnancy supports the expansion of Treg clonotypes that are equipped to recognize EAE-associated Ags. These Treg are thereby particularly suited to control corresponding encephalitogenic Tcon responses and likely contribute to pregnancy-associated protection in autoimmunity.
自身免疫性疾病（如多发性硬化症）及其小鼠模型实验性自身免疫性脑脊髓炎（EAE）的疾病活动会暂时受到妊娠的抑制。然而，疾病的改善是由于非特异性免疫调节还是由于 Ag 特异性调节致病常规 T 细胞（Tcon）和免疫抑制性调节 T 细胞（Treg）仍不清楚。在本研究中，我们使用 TCR 测序系统地分析了 EAE 和妊娠驱动的 TCRβ 库的变化。我们证明，EAE 而非妊娠会强烈增加外周 Tcon 和 Treg 中 TCR 库克隆性。值得注意的是，妊娠对于携带优势 EAE 相关 TRBV13-2 链的 Treg 的扩增是必需的，并增加了 Treg 中与 EAE 相关的克隆型的频率。我们的研究结果表明，妊娠支持能够识别 EAE 相关 Ag 的 Treg 克隆型的扩增。这些 Treg 特别适合控制相应的致脑炎 Tcon 反应，可能有助于自身免疫中的妊娠相关保护。
