Senger Stefania, Luongo Diomira, Maurano Francesco, Mazzeo Maria F, Siciliano Rosa A, Gianfrani Carmela, David Chella, Troncone Riccardo, Auricchio Salvatore, Rossi Mauro
Istituto di Scienze dell' Alimentazione, CNR, via Roma 52, 83100 Avellino, Italy.
Immunol Lett. 2003 Aug 5;88(2):127-34. doi: 10.1016/s0165-2478(03)00069-5.
The mucosal lesion in coeliac disease (CD) is an immune-mediated injury triggered by gliadin and associated with HLA-DQ2 and HLA-DQ8. In view of this, an approach that re-induces tolerance to this antigen should be considered as possible alternative to a strict gluten-free diet in treating CD. However, T-cell activation to multiple antigens, as a consequence of the chemical complexity shown by the antigen gliadin, could hamper the efforts to identify single component(s) useful for tolerance induction. To address this issue, a recombinant alpha-gliadin was tested in tolerance experiments in HLA-DQ8 transgenic mice. As tissue transglutaminase (tTG) treatment of gliadin, previously reported to enhance its stimulatory activity in CD, did not increase its immunogenicity when parenterally administered in these mice, untreated gliadin was used as immunogen. A decrease in systemic T cell responses to the recombinant alpha-gliadin was found after nasal administration of antigen, reflected by lymphocytes proliferation assay. Interestingly, while the immunisation protocol induced transcription of both Th1 (IFN-gamma) and Th2 (IL-4 and IL-10) cytokines, the tolerisation protocol down-regulated significantly only the IFN-gamma mRNA expression. More important, the recombinant alpha-gliadin induced a similar down-regulatory effect in mice immunised with a commercial preparation of wheat gliadin, that is a mixture of many different gliadin components. As the Th1 phenotype and the HLA-DQ8 molecule play a role in the pathogenesis of CD, our data underlined the potential usefulness of this recombinant protein for the immunomodulation of this disease.
乳糜泻（CD）中的黏膜病变是由麦醇溶蛋白引发的免疫介导损伤，与HLA - DQ2和HLA - DQ8相关。鉴于此，在治疗CD时，重新诱导对该抗原的耐受性的方法应被视为严格无麸质饮食的一种可能替代方案。然而，由于麦醇溶蛋白抗原表现出的化学复杂性，T细胞对多种抗原的激活可能会阻碍识别有助于诱导耐受性的单一成分的努力。为了解决这个问题，在HLA - DQ8转基因小鼠的耐受性实验中对重组α - 麦醇溶蛋白进行了测试。由于先前报道组织转谷氨酰胺酶（tTG）处理麦醇溶蛋白可增强其在CD中的刺激活性，但在这些小鼠中经肠胃外给药时并未增加其免疫原性，因此使用未处理的麦醇溶蛋白作为免疫原。经鼻腔给予抗原后，发现全身性T细胞对重组α - 麦醇溶蛋白的反应降低，这通过淋巴细胞增殖试验得以体现。有趣的是，虽然免疫方案诱导了Th1（IFN - γ）和Th2（IL - 4和IL - 10）细胞因子的转录，但耐受方案仅显著下调了IFN - γ mRNA的表达。更重要的是，重组α - 麦醇溶蛋白在用商业制备的小麦麦醇溶蛋白（即许多不同麦醇溶蛋白成分的混合物）免疫的小鼠中诱导了类似的下调作用。由于Th1表型和HLA - DQ8分子在CD的发病机制中起作用，我们的数据强调了这种重组蛋白对该疾病进行免疫调节的潜在有用性。
