Centre for Immune Regulation and Department of Immunology, Oslo University Hospital-Rikshospitalet, Oslo, Norway; Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway; PreventCD Project Group.
Centre for Immune Regulation and Department of Immunology, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
Gastroenterology. 2017 Sep;153(3):787-798.e4. doi: 10.1053/j.gastro.2017.05.016. Epub 2017 May 20.
BACKGROUND & AIMS: Celiac disease is a chronic small intestinal inflammatory disorder mediated by an immune response to gluten peptides in genetically susceptible individuals. Celiac disease is often diagnosed in early childhood, but some patients receive a diagnosis late in life. It is uncertain whether pediatric celiac disease is distinct from adult celiac disease. It has been proposed that gluten-reactive T cells in children recognize deamidated and native gluten epitopes, whereas T cells from adults only recognize deamidated gluten peptides. We studied the repertoire of gluten epitopes recognized by T cells from children and adults.
We examined T-cell responses against gluten by generating T-cell lines and T-cell clones from intestinal biopsies of adults and children and tested proliferative response to various gluten peptides. We analyzed T cells from 14 children (2-5 years old) at high risk for celiac disease who were followed for celiac disease development. We also analyzed T cells from 6 adults (26-55 years old) with untreated celiac disease. All children and adults were positive for HLA-DQ2.5. Biopsies were incubated with gluten digested with chymotrypsin (modified or unmodified by the enzyme transglutaminase 2) or the peptic-tryptic digest of gliadin (in native and deamidated forms) before T-cell collection.
Levels of T-cell responses were higher to deamidated gluten than to native gluten in children and adults. T cells from children and adults each reacted to multiple gluten epitopes. Several T-cell clones were cross-reactive, especially clones that recognized epitopes from γ-and ω-gliadin. About half of the generated T-cell clones from children and adults reacted to unknown epitopes.
T-cell responses to different gluten peptides appear to be similar between adults and children at the time of diagnosis of celiac disease.
乳糜泻是一种由遗传易感性个体对麸质肽的免疫反应介导的慢性小肠炎症性疾病。乳糜泻通常在儿童早期诊断，但有些患者在生命后期才被诊断出来。目前尚不清楚小儿乳糜泻是否与成人乳糜泻不同。有人提出，儿童的麸质反应性 T 细胞识别脱酰胺和天然麸质表位，而成人的 T 细胞仅识别脱酰胺的麸质肽。我们研究了儿童和成人 T 细胞识别的麸质表位谱。
我们从成人和儿童的肠道活检中生成 T 细胞系和 T 细胞克隆，研究 T 细胞对麸质的反应，并测试对各种麸质肽的增殖反应，以此来检测 T 细胞对麸质的反应。我们检测了 14 名（2-5 岁）高风险乳糜泻儿童的 T 细胞，这些儿童正在接受乳糜泻发病的随访。我们还分析了 6 名（26-55 岁）未经治疗的乳糜泻成人的 T 细胞。所有儿童和成人均为 HLA-DQ2.5 阳性。在收集 T 细胞之前，将活检标本与胰凝乳蛋白酶消化的（酶转谷氨酰胺酶 2 修饰或未修饰）或（天然和脱酰胺形式）肽-胰蛋白酶消化的麦醇溶蛋白孵育。
儿童和成人对脱酰胺麸质的 T 细胞反应水平均高于对天然麸质的反应水平。儿童和成人的 T 细胞均对多个麸质表位有反应。一些 T 细胞克隆具有交叉反应性，尤其是那些识别 γ-和 ω-麦醇溶蛋白表位的克隆。从儿童和成人生成的约一半 T 细胞克隆对未知表位有反应。
在诊断乳糜泻时，儿童和成人的不同麸质肽的 T 细胞反应似乎相似。
