Plasma Cells Are the Most Abundant Gluten Peptide MHC-expressing Cells in Inflamed Intestinal Tissues From Patients With Celiac Disease
Plasma Cells Are the Most Abundant Gluten Peptide MHC-expressing Cells in Inflamed Intestinal Tissues From Patients With Celiac Disease
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DOI：
10.1053/j.gastro.2018.12.013
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发表时间：
2019-04-01
期刊：
影响因子：
29.4
通讯作者：
Loset, Geir Age
中科院分区：
文献类型：
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作者：
Hoydahl, Lene Stokken;Richter, Lisa;Loset, Geir Age
背景与目的：乳糜泻的发展被认为与特定HLA-DQ单倍型个体肠黏膜中CD4(+) T细胞对脱酰胺谷蛋白肽的转谷氨酰胺酶依赖性反应有关。我们研究了这种粘膜免疫反应中的抗原呈递过程。方法：我们利用噬菌体展示技术制备了针对HLA-DQ2.5肽- mhc （pMHC）复合物和免疫优势谷蛋白表位DQ2.5-glia-alpha 1a的单克隆抗体（mab）。我们使用这些单克隆抗体，通过流式细胞术和酶联免疫吸收点（ELISPOT），在40例乳糜泻患者（35例未经治疗，5例无麸质饮食）和18例确认无炎症肠道粘膜的受试者（对照组，12例推定健康，5例接受胰十二指肠切除术，1例可能患有乳糜泻）的肠道活检中新鲜制备的单细胞悬液中评估麸质肽的呈现和呈递细胞的表型。结果：使用单克隆抗体，我们在食用谷蛋白的乳糜泻患者的肠道活检细胞中检测到MHC复合物，但在无谷蛋白饮食的患者中检测不到。我们发现B细胞和浆细胞是炎症粘膜中表达dq2.5 -胶质α 1a最多的细胞。我们发现了一个浆细胞亚群，表达针对谷蛋白肽或自身抗原转谷氨酰胺酶2 （TG2）特异性的b细胞受体（BCR）。MHCII类（MHCII）的表达并不局限于乳糜泻患者的这些特异性浆细胞，但在患者和对照组的平均30%的肠道浆细胞中观察到。结论：乳糜泻患者肠道活检的浆细胞表达MHCII；这是这些患者组织中最丰富的细胞类型，呈现免疫优势谷蛋白肽DQ2.5-glia-a1a。这些结果表明，肠道中的浆细胞可以作为抗原提呈细胞，并可能促进和维持乳糜泻或其他炎症性疾病患者的肠道炎症。
BACKGROUND & AIMS: Development of celiac disease is believed to involve the transglutaminase-dependent response of CD4(+) T cells toward deamidated gluten peptides in the intestinal mucosa of individuals with specific HLA-DQ haplotypes. We investigated the antigen presentation process during this mucosal immune response. METHODS: We generated monoclonal antibodies (mAbs) specific for the peptide-MHC (pMHC) complex of HLA-DQ2.5 and the immunodominant gluten epitope DQ2.5-glia-alpha 1a using phage display. We used these mAbs to assess gluten peptide presentation and phenotypes of presenting cells by flow cytometry and enzyme-linked immune absorbent spot (ELISPOT) in freshly prepared single-cell suspensions from intestinal biopsies from 40 patients with celiac disease (35 untreated and 5 on a gluten-free diet) as well as 18 subjects with confirmed noninflamed gut mucosa (controls, 12 presumed healthy, 5 undergoing pancreatoduodenectomy, and 1 with potential celiac disease). RESULTS: Using the mAbs, we detected MHC complexes on cells from intestinal biopsies from patients with celiac disease who consume gluten, but not from patients on gluten-free diets. We found B cells and plasma cells to be the most abundant cells that present DQ2.5-glia-alpha 1a in the inflamed mucosa. We identified a subset of plasma cells that expresses B-cell receptors (BCR) specific for gluten peptides or the autoantigen transglutaminase 2 (TG2). Expression of MHC class II (MHCII) was not restricted to these specific plasma cells in patients with celiac disease but was observed in an average 30% of gut plasma cells from patients and controls. CONCLUSIONS: A population of plasma cells from intestinal biopsies of patients with celiac disease express MHCII; this is the most abundant cell type presenting the immunodominant gluten peptide DQ2.5-glia-a1a in the tissues from these patients. These results indicate that plasma cells in the gut can function as antigen-presenting cells and might promote and maintain intestinal inflammation in patients with celiac disease or other inflammatory disorders.