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瑞士苏黎世联邦理工学院D. Latorre团队发现，吉兰-巴雷综合征中的自反应T细胞靶向周围神经。相关论文于2024年1月17日在线发表在《自然》杂志上。

研究人员表示，吉兰-巴雷综合征（Guillain-Barré Syndrome，GBS）是一种罕见的外周神经系统异质性疾病，通常由先前的感染诱发，并导致可能危及生命的进行性肌无力。虽然GBS被认为是一种自身免疫性疾病，但其不同临床亚型的发病机制在很大程度上仍不为人所知。

研究人员通过体外T细胞筛选、单细胞RNA测序和T细胞受体（TCR）测序相结合的方法，在脱髓鞘疾病变异型患者中鉴定出了表现出细胞毒性T辅助细胞1（T_H1）样表型的自反应记忆CD4⁺细胞，以及靶向周围神经髓鞘抗原的罕见CD8⁺ T细胞。研究人员对1000多个自身反应性单个T细胞克隆进行了鉴定，发现它们具有多克隆TCR反应谱、短CDR3β长度、优先HLA-DR限制和识别免疫优势表位。

研究人员发现，自身反应性TCRβ克隆型在同一患者不同疾病阶段的血液中扩张，值得注意的是，它们在不同GBS患者的血液和脑脊液中共享，而在对照组个体中则没有。最后，研究人员在一名患者的神经活检中发现了髓鞘反应T细胞，这表明这些细胞直接参与了疾病的病理生理学。总之，这些数据提供了GBS患者中自身反应性T细胞免疫的明确证据，并为炎症性周围神经病领域开辟了新的视角，对生物医学应用具有潜在影响。

附：英文原文

Title: Autoreactive T cells target peripheral nerves in Guillain–Barré syndrome

Author: Skenkov, L., Mallone, A., Schreiner, B., Ripellino, P., Nilsson, J., Stoffel, M., Ulbrich, S. E., Sallusto, F., Latorre, D.

Issue&Volume: 2024-01-17

Abstract: Guillain–Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that underlie its distinct clinical subtypes remain largely unknown. Here, by combining in vitro T cell screening, single-cell RNA sequencing and T cell receptor (TCR) sequencing, we identify autoreactive memory CD4+ cells, that show a cytotoxic T helper 1 (TH1)-like phenotype, and rare CD8+ T cells that target myelin antigens of the peripheral nerves in patients with the demyelinating disease variant. We characterized more than 1,000 autoreactive single T cell clones, which revealed a polyclonal TCR repertoire, short CDR3β lengths, preferential HLA-DR restrictions and recognition of immunodominant epitopes. We found that autoreactive TCRβ clonotypes were expanded in the blood of the same patient at distinct disease stages and, notably, that they were shared in the blood and the cerebrospinal fluid across different patients with GBS, but not in control individuals. Finally, we identified myelin-reactive T cells in the nerve biopsy from one patient, which indicates that these cells contribute directly to disease pathophysiology. Collectively, our data provide clear evidence of autoreactive T cell immunity in a subset of patients with GBS, and open new perspectives in the field of inflammatory peripheral neuropathies, with potential impact for biomedical applications. Autoreactive T cells that target myelin antigens in the peripheral nerves are present in patients with the demyelinating form of Guillain–Barré syndrome, and these T cells are likely to contribute to disease pathophysiology.

DOI: 10.1038/s41586-023-06916-6

Source: https://www.nature.com/articles/s41586-023-06916-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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