To understand the role of T cells in the pathogenesis of ulcerative colitis (UC), we analyzed colonic T cells isolated from patients with UC and controls. Here we identified colonic CD4⁺ and CD8⁺ T lymphocyte subsets with gene expression profiles resembling stem-like progenitors, previously reported in several mouse models of autoimmune disease. Stem-like T cells were increased in inflamed areas compared to non-inflamed regions from the same patients. Furthermore, TCR sequence analysis indicated stem-like T cells were clonally related to proinflammatory T cells, suggesting their involvement in sustaining effectors that drive inflammation. Using an adoptive transfer colitis model in mice, we demonstrated that CD4⁺ T cells deficient in either BCL-6 or TCF1, transcription factors that promote T cell stemness, had decreased colon T cells and diminished pathogenicity. Our results establish a strong association between stem-like T cell populations and UC pathogenesis, highlighting the potential of targeting this population to improve clinical outcomes.

为了了解 T 细胞在溃疡性结肠炎 (UC) 发病机制中的作用，我们分析了从 UC 患者和对照组中分离的结肠 T 细胞。在这里，我们鉴定了结肠 CD4 ⁺和 CD8 ⁺ T 淋巴细胞亚群，其基因表达谱类似于干细胞样祖细胞，先前在几种自身免疫性疾病小鼠模型中报道过。与同一患者的非发炎区域相比，发炎区域的干细胞样 T 细胞有所增加。此外，TCR 序列分析表明干细胞样 T 细胞与促炎性 T 细胞克隆相关，表明它们参与维持驱动炎症的效应子。使用小鼠过继性转移性结肠炎模型，我们证明缺乏 BCL-6 或 TCF1（促进 T 细胞干性的转录因子）的 CD4 ⁺ T 细胞会减少结肠 T 细胞并降低致病性。我们的结果建立了干细胞样 T 细胞群与 UC 发病机制之间的密切关联，强调了针对该群体改善临床结果的潜力。