Molberg O, Lundin K E, Nilsen E M, Scott H, Kett K, Brandtzaeg P, Thorsby E, Sollid L M
Institute of Transplantation Immunology, The National Hospital, University of Oslo, Norway.
Tissue Antigens. 1998 Nov;52(5):407-15. doi: 10.1111/j.1399-0039.1998.tb03066.x.
Celiac disease is a common HLA-DQ2-associated enteropathy caused by an abnormal T-cell-mediated immune response to ingested wheat gliadin proteins. We have previously isolated in situ activated mucosal T cells from celiac disease patients and demonstrated that these T cells were gliadin specific and predominantly DQ2 restricted. In contrast to this, gliadin-specific T cells isolated from peripheral blood display a variable HLA restriction pattern, thereby indicating that the skewed DQ restriction of T cells resident in the celiac lesions could be dictated by a preference for DQ-mediated antigen presentation in the mucosa of CD patients. To address this, we analyzed the HLA restriction of T cells recognizing astrovirus, a common gastroentetitis virus, isolated from intestinal mucosa of six celiac disease patients. As an internal control, gliadin-specific T cells were isolated and analyzed in parallel. The gliadin-specific mucosal T cells were marked in their DQ2 restriction, whereas the parallel astrovirus-specific T cells were predominantly restricted by DR molecules. Our data indicate that the repertoire of T cells present in celiac lesions is determined by the priming antigen(s) and not by a skewing in the expression of functional HLA class II isotypes in the disease affected small intestinal mucosa.
乳糜泻是一种常见的与HLA-DQ2相关的肠病，由对摄入的小麦醇溶蛋白的异常T细胞介导的免疫反应引起。我们之前从乳糜泻患者中分离出原位活化的黏膜T细胞，并证明这些T细胞对醇溶蛋白具有特异性，且主要受DQ2限制。与此相反，从外周血中分离出的醇溶蛋白特异性T细胞表现出可变的HLA限制模式，从而表明乳糜泻病变部位驻留的T细胞的偏态DQ限制可能是由CD患者黏膜中对DQ介导的抗原呈递的偏好所决定的。为了解决这个问题，我们分析了从6名乳糜泻患者的肠黏膜中分离出的识别星状病毒（一种常见的胃肠炎病毒）的T细胞的HLA限制。作为内部对照，则平行分离并分析醇溶蛋白特异性T细胞。醇溶蛋白特异性黏膜T细胞表现出DQ2限制，而平行的星状病毒特异性T细胞主要受DR分子限制。我们的数据表明，乳糜泻病变部位存在的T细胞库是由引发抗原决定的，而不是由疾病累及的小肠黏膜中功能性HLA-II类同种型表达的偏态决定的。
