Turley Shannon, Poirot Laurent, Hattori Masakazu, Benoist Christophe, Mathis Diane
Section of Immunology and Immunogenetics, Joslin Diabetes Center and Dept. of Medicine, Brigham and Women's Hospital, Harvard Medical School, One Joslin Pl., Boston, MA 02215, USA.
J Exp Med. 2003 Nov 17;198(10):1527-37. doi: 10.1084/jem.20030966.
The prelude to type-1 diabetes is leukocyte infiltration into the pancreatic islets, or insulitis. This process begins in pancreatic lymph nodes when T lymphocytes reactive to islet beta cells encounter antigen-presenting cells (APCs) displaying peptides derived from beta cell proteins. We show here that a ripple of physiological beta cell death, which occurs at 2 wk of age in all mouse strains, precipitates the arrival of such APCs, and that the relevant APC is a dendritic cell of CD11c+CD11b+CD8alpha- phenotype. These findings have significant implications concerning the nature of the diabetes-provoking deficits in NOD mice, the identity of the primordial diabetogenic antigens, and our understanding of the balance between immunity and tolerance in a pathological context.
1型糖尿病的前奏是白细胞浸润胰岛，即胰岛炎。当对胰岛β细胞有反应的T淋巴细胞遇到呈递源自β细胞蛋白的肽段的抗原呈递细胞（APC）时，这个过程在胰腺淋巴结中开始。我们在此表明，在所有小鼠品系中2周龄时发生的生理性β细胞死亡波动促使此类APC的到来，并且相关的APC是具有CD11c + CD11b + CD8α-表型的树突状细胞。这些发现对于NOD小鼠中引发糖尿病的缺陷的性质、原发性致糖尿病抗原的身份以及我们对病理背景下免疫与耐受平衡的理解具有重要意义。
