Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; National Translational Science Center for Molecular Medicine & Department of Cell Biology, The Fourth Military Medical University, Xi'an 710032, China; Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850, China.
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
EBioMedicine. 2019 Sep;47:414-426. doi: 10.1016/j.ebiom.2019.07.032. Epub 2019 Aug 30.
Ankylosing spondylitis (AS) is a chronic inflammatory disease with worldwide high prevalence. Although AS is strongly associated with HLA-B27 MHC-I antigen presentation, the role played by αβ T cells in AS remains elusive.
Utilizing TCRβ repertoire sequencing and bioinformatics tools developed in house, we analyzed overall TCR repertoire structures and antigen-recognizing CDR3 motifs in AS patients with different disease activities.
We found that disease progression is associated with both CD4+ and CD8+ T cell oligo-clonal expansion, which suggests that αβ T cell activation may mediate AS disease progression. By developing a bioinformatics platform to dissect antigen-specific responses, we discovered a cell population consisting of both CD4+ and CD8+ T cells expressing identical TCRs, herein termed CD4/8 T cells. CD4/8 clonotypes were highly enriched in the spondyloarthritic joint fluid of patients, and their expansion correlated with the activity of disease.
These results provide evidence on the T cell clone side to reveal the potential role of CD4/8 T cells in the etiology of AS development.
强直性脊柱炎（AS）是一种具有全球高患病率的慢性炎症性疾病。尽管 AS 与 HLA-B27 MHC-I 抗原呈递密切相关，但αβ T 细胞在 AS 中的作用仍不清楚。
利用 TCRβ 库测序和内部开发的生物信息学工具，我们分析了不同疾病活动度的 AS 患者的总体 TCR 库结构和抗原识别的 CDR3 基序。
我们发现疾病进展与 CD4+和 CD8+ T 细胞的寡克隆扩增有关，这表明αβ T 细胞的激活可能介导了 AS 的疾病进展。通过开发一个用于剖析抗原特异性反应的生物信息学平台，我们发现了一群同时表达相同 TCR 的 CD4+和 CD8+ T 细胞，在此称为 CD4/8 T 细胞。CD4/8 克隆型在患者的脊柱关节炎关节液中高度富集，其扩增与疾病的活动度相关。
这些结果从 T 细胞克隆的角度提供了证据，揭示了 CD4/8 T 细胞在 AS 发病机制中的潜在作用。
