Disease heterogeneity hampers achieving long-term disease remission in inflammatory bowel disease (IBD). Monitoring ongoing tissue-localized regulatory and inflammatory T-cell responses in peripheral blood would empower disease classification. We determined whether regulatory and inflammatory phenotypes of circulating CD38⁺ effector (CD62L^negCD4⁺) T cells, a population enriched for cells with mucosal antigen specificity, classify disease course in pediatric IBD patients. In healthy individuals, circulating CD38⁺ effector T cells had a predominant regulatory component with lower frequencies of IFNγ-secreting T cells, higher frequencies of IL-10-secreting T cells and higher frequencies of inhibitory molecule T-cell immunoglobulin and ITIM domain⁺ (TIGIT) cells than CD38^neg effector T cells. TIGIT expression was stable upon stimulation and marked CD38⁺ T cells with inhibitory properties. In IBD patients with active intestinal inflammation this predominant regulatory component was lost: circulating CD38⁺ effector T cells had increased activated CD25⁺CD45RA^neg and decreased TIGIT⁺ cell frequencies. TIGIT percentages below 25% before treatment associated with shorter duration of clinical remission. In conclusion, phenotypic changes in circulating CD38⁺ effector T cells, in particular the frequency of TIGIT⁺ cells, classify pediatric IBD patients and predict severity of disease course. These findings have relevance for IBD and can be exploited in graft-versus-host-disease and checkpoint inhibitor-induced inflammation in cancer.

中文翻译：

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循环调节性 TIGIT+CD38+ 效应 T 细胞的频率与炎症性肠病的病程相关。

疾病异质性阻碍了炎症性肠病 (IBD) 的长期疾病缓解。监测外周血中正在进行的组织局部调节和炎症 T 细胞反应将有助于疾病分类。我们确定了循环 CD38 ⁺效应子（CD62L^负CD4 ⁺）T 细胞（富含具有粘膜抗原特异性的细胞群）的调节和炎症表型是否对小儿 IBD 患者的病程进行分类。在健康个体中，循环 CD38 ^{+效应 T 细胞具有主要的调节成分，与 CD38阴性}效应细胞相比，分泌 IFNγ 的 T 细胞频率较低，分泌 IL-10 的 T 细胞频率较高，抑制分子 T 细胞免疫球蛋白和 ITIM 结构域⁺ (TIGIT) 细胞的频率较高T 细胞。TIGIT 表达在刺激后稳定，并标记 CD38 ⁺ T 细胞具有抑制特性。在患有活动性肠道炎症的 IBD 患者中，这种主要的调节成分丢失了：循环 CD38 ⁺效应 T 细胞增加了活化的 CD25 ⁺ CD45RA ^neg并减少了 TIGIT ⁺细胞频率。治疗前 TIGIT 百分比低于 25% 与较短的临床缓解持续时间相关。总之，循环 CD38 ⁺效应 T 细胞的表型变化，特别是 TIGIT ⁺细胞的频率，对小儿 IBD 患者进行分类并预测病程的严重程度。这些发现与 IBD 相关，可用于移植物抗宿主病和检查点抑制剂诱导的癌症炎症。