乳糜泻患者麸质激发试验后外周血T细胞的改变

作     者：Anderson R.P. Van Heel D.A. Tye- Din J.A. 尹勇 

作者机构：Autoimmunity and Transplantation Division Walter and Eliza Hall Institute c/o Post Office RMH Parkville Vic. 3050 Australia Dr. 

出 版 物：《世界核心医学期刊文摘（胃肠病学分册）》 (Core Journals in Gastroenterology)

年 卷 期：2005年第1卷第12期

页      面：34-34页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：乳糜泻 激发试验 麸质 细胞克隆 细胞免疫应答 抗原决定簇 外周血单核细胞 酶联免疫斑点法 ELISPOT γ干扰素 

摘      要：Background: Current understanding of T cell epitopes in coeliac disease (CD) largely derives from intestinal T cell clones in vitro. T cell clones allow identification of gluten peptides that stimulate T cells but do not quantify their contribution to the overall gluten specific T cell response in individuals with CD when exposed to gluten in vivo. Aims: To determine the contribution of a putative dominant T cell epitope to the overall gliadin T cell response in HLA- DQ2 CD in vivo. Patients: HLA- DQ2+ individuals with CD and healthy controls. Methods: Subjects consumed 20 g of gluten daily for three days. Interferon γ (IFN- γ ) ELISPOT was performed using peripheral blood mononuclear cells (PBMC) to enumerate and characterise peptide and gliadin specific T cells before and after gluten challenge. Results: In 50/59 CD subjects, irrespective of homo- or heterozygosity for HLA- DQ2, IFN- γ ELISPOT responses for an optimal concentration of A- gliadin 57- 73 Q- E65 were between 10 and 1500 per million PBMC, equivalent to a median 51% of the response for a “ near optimal concentration of deamidated gliadin. Whole deamidated gliadin and gliadin epitope specific T cells induced in peripheral blood expressed an intestinal homing integrin (α 4β 7) and were HLA- DQ2 restricted. Peripheral blood T cells specific for A- gliadin 57- 73 Q- E65 are rare in untreated CD but can be predictably induced two weeks after gluten exclusion. Conclusion: In vivo gluten challenge is a simple safe method that allows relevant T cells to be analysed and quantified in peripheral blood by ELISPOT, and should permit comprehensive high throughput mapping of gluten T cell epitopes in large numbers of individuals with CD.