Iro Mildred A, Rollier Christine S, Irani Sarosh R, Sadarangani Manish, Al-Diwani Adam, Pollard Andrew J, Clutterbuck Elizabeth A
Faculty of Medicine and Institute of Life Sciences, University of Southampton, United Kingdom.
Department of Paediatric Infectious Diseases, Southampton Children's Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Encephalitis. 2023 Jan;3(1):15-23. doi: 10.47936/encephalitis.2022.00052. Epub 2023 Jan 3.
Purpose Regulatory T cells (Tregs) have been implicated in the pathogenesis of several autoimmune disorders and used in adoptive cell transfer therapies. Neither have been explored in patients with autoimmune encephalitis where treated patient outcomes remain suboptimal with frequent relapses. Here, to identify new treatment strategies for autoimmune encephalitis, we sought to evaluate the proportion of circulating Tregs and Treg subpopulations in peripheral blood of patients with -methyl-ᴅ-aspartate receptor-antibody encephalitis (NMDAR-Ab-E) and compared this with healthy controls.
We compared the phenotype of peripheral blood Tregs in four adult NMDAR-Ab-E patients and four age- and sex-matched healthy controls using an 11-color flow cytometry assay panel for characterization of Tregs (CD4+ CD25+ FoxP3+) cells into naïve (chemokine receptor [CCR] 7+ CD45RA+), central memory (CCR7+ CD45RA-), and effector memory (CCR7- CD45RA-) cells. We also examined and compared the expression of the CCR6 by circulating Tregs and the respective Treg subpopulations between the study groups.
The proportion of circulating Tregs was similar between patients with NMDAR-Ab-E and healthy controls but the proportion of naïve Tregs was lower in NMDAR-Ab-E patients (p = 0.0026). Additionally, the frequency of circulating effector memory Tregs was higher, and the proportion of circulating effector memory Tregs expressing CCR6 was lower, in NMDAR-Ab-E patients compared with healthy controls (p = 0.0026).
Altered Treg homeostasis may be a feature of patients with NMDAR-Ab-E. Future studies with larger samples are warranted to validate these findings.
调节性T细胞（Tregs）与多种自身免疫性疾病的发病机制有关，并用于过继性细胞转移疗法。在自身免疫性脑炎患者中，这两方面均未得到探索，此类患者的治疗效果仍不理想，且频繁复发。在此，为了确定自身免疫性脑炎的新治疗策略，我们试图评估抗N-甲基-D-天冬氨酸受体抗体脑炎（NMDAR-Ab-E）患者外周血中循环Tregs及其亚群的比例，并将其与健康对照进行比较。
我们使用11色流式细胞术检测面板，比较了4例成年NMDAR-Ab-E患者和4例年龄及性别匹配的健康对照外周血Tregs的表型，以将Tregs（CD4+ CD25+ FoxP3+）细胞分为初始（趋化因子受体[CCR] 7+ CD45RA+）、中央记忆（CCR7+ CD45RA-）和效应记忆（CCR7- CD45RA-）细胞。我们还检测并比较了研究组之间循环Tregs及其各自亚群中CCR6的表达。
NMDAR-Ab-E患者与健康对照之间循环Tregs的比例相似，但NMDAR-Ab-E患者中初始Tregs的比例较低（p = 0.0026）。此外，与健康对照相比，NMDAR-Ab-E患者中循环效应记忆Tregs的频率较高，而表达CCR6的循环效应记忆Tregs的比例较低（p = 0.0026）。
Treg稳态改变可能是NMDAR-Ab-E患者的一个特征。有必要进行更大样本量的未来研究来验证这些发现。
