Immunological study of autoimmune pancreatitis

我们观察到抗核抗体(ANA)、抗乳铁蛋白抗体(ALF)、抗碳酸氢酶-II(CA-II)抗体(ACA-II)、类风湿因子(RA)和抗平滑肌抗体(ACA-II)等自身抗体在慢性支气管炎患者中的检出频率较高。这些抗体的高流行率提示CA-II和LF可能是AIP的靶抗原。尽管AIP的效应细胞尚不清楚，但与其他原因的胰腺炎(如酒精性或胆石性胰腺炎)相比，AIP患者外周血淋巴细胞(PBL)中具有HLA-DR和CD45RO的活化的CD4+和CD8+T细胞明显增加。在胰腺组织中，CD4+T细胞也比CD8+T细胞更有优势地渗透。与SjS或PSC相似，表现Th1型免疫反应的CD4+T细胞主要参与AIP作为效应细胞的发展，而不是Th2型CD4+T细胞。在一些急性间质性肺炎患者中，人类白细胞抗原-DR抗原为…更多的Re表达在胰管细胞和CD4+T细胞上。经CA-II或LF皮下免疫的新生胸腺切除(NTX)小鼠和经疾病诱导的NTX小鼠的脾细胞移植的协同裸小鼠发生了胰腺炎、涎腺炎和胆管炎，而正常Bala/c小鼠则没有。在我们用NTX-BALB/c小鼠和移植的裸鼠建立的动物模型中，CD4阳性细胞主要参与胰腺炎、涎腺炎和胆管炎的发生，而CD8+T细胞从未致病。提示MHC-II类限制性自身反应性CD4+T细胞逃避胸腺的负性选择，以及外周调节性T细胞如CD25+T细胞的耗竭在自身免疫性胰腺炎和外分泌病的发生发展中起重要作用。这些动物模型表明，虽然CD8+T细胞可能有部分参与，但CD4+T细胞在实验性胰腺炎的发生发展中起主要作用，这与人类AIP是一致的。较少

We observed that several autoantibodies such as antinuclear antibody (ANA), anti-lactoferrin (LF) antibody (ALF), anti-carbonic anhydrase-II (CA-II) antibody (ACA-II ), rheumatoid factor and antismooth muscle antibody were frequently detected in patients with. The high prevalence of these antibodies suggests that CA-II and LF may be the candidates for the target antigens in AIP.Although the effector cells of AIP have been poorly understood, the activated CD4+ and CD8+ T-cells bearing HLA-DR and CD45RO were increased in the peripheral blood lymphocytes (PBLs) in the patients with AIP in comparison with those in other causes of pancreatitis such as alcoholic or gallstone-related pancreatitis. CD4+ T-cells also predominantly infiltrate in the pancreas tissue over CD8+ T-cells. Similar to SjS or PSC, CD4+ T-cells showing Th1 type of immune response are predominantly involved in the development of AIP as effector cells over Th2 type CD4+ T-cells. In some patients with AIP, HLA-DR antigens a … More re expressed on the pancreatic duct cells as well as CD4+ T-cells. Neonatally thymectomized (nTx) mice subcutaneally immunized with CA-II or LF, and synergetic nude mice, transferred with seplenocytes from the disease-induced nTx-mice, developed pancreatitis as well as sialoadenitis and cholangitis, but the normal BALA/c mice did not. In our animal model using nTx-BALB/c mice and transferred nude mice, the CD4-positive cells were mainly involved in the development of pancreatitis, sialoadenitis and cholangitis, while CD8+ T-cells were never pathogenic. These findings suggested that MHC-class II restricted-autoreactive CD4+T-cells, which escape from the negative selection in the thymus, and depletion of regulatory T-cells such as CD25+ T-cells in the periphery take important roles in the development of autoimmune pancreatitis and exocrinopathy. These animal models suggest that although CD8+ T-cells may be partially involved, CD4+ T-cells take major roles in the development of experimental pancreatitis, which is consistent with human AIP. Less