Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; HS Diagnomics GmbH, Berlin, Germany.
HS Diagnomics GmbH, Berlin, Germany.
Clin Immunol. 2023 Nov;256:109795. doi: 10.1016/j.clim.2023.109795. Epub 2023 Sep 27.
Celiac disease (CeD) is an autoimmune disorder affecting the small intestine with gluten as disease trigger. Infections including Influenza A, increase the CeD risk. While gluten-specific CD4 T-cells, recognizing HLA-DQ2/DQ8 presented gluten-peptides, initiate and sustain the celiac immune response, CD8 α/β intraepithelial T-cells elicit mucosal damage. Here, we subjected TCRs from a cohort of 56 CeD patients and 22 controls to an analysis employing 749 published CeD-related TCRβ-rearrangements derived from gluten-specific CD4 T-cells and gluten-triggered peripheral blood CD8 T-cells. We show, that in addition to TCRs from gluten-specific CD4 T-cells, TCRs of gluten-triggered CD8 T-cells are significantly enriched in CeD duodenal tissue samples. TCRβ-rearrangements of gluten-triggered CD8 T-cells were even more expanded in patients than TCRs from gluten-specific CD4 T-cells (p < 0.0002) and highest in refractory CeD. Sequence alignments with TCR-antigen databases suggest that a subgroup of these most likely indirectly gluten-triggered TCRs recognize microbial, viral, and autoantigens.
乳糜泻（CeD）是一种影响小肠的自身免疫性疾病，其病因为麸质。包括流感 A 在内的感染会增加乳糜泻的风险。虽然识别 HLA-DQ2/DQ8 呈递的麸质肽的特异性 CD4 T 细胞会引发和维持乳糜泻免疫反应，但 CD8α/β 上皮内 T 细胞会引发黏膜损伤。在这里，我们对来自 56 名乳糜泻患者和 22 名对照者的 TCR 进行了分析，该分析使用了来自于乳糜泻患者的特异性 CD4 T 细胞和由麸质触发的外周血 CD8 T 细胞中的 749 个已发表的 TCRβ 重排。我们表明，除了来自于乳糜泻患者的特异性 CD4 T 细胞的 TCR 之外，由麸质触发的 CD8 T 细胞的 TCR 也明显富集在乳糜泻十二指肠组织样本中。与乳糜泻患者的特异性 CD4 T 细胞的 TCR 相比，来自于由麸质触发的 CD8 T 细胞的 TCRβ 重排更多地扩增（p<0.0002），在难治性乳糜泻中最为显著。与 TCR 抗原数据库的序列比对表明，这些 TCR 中的一个亚组可能间接识别微生物、病毒和自身抗原。
