Hepatitis resulting from liver-specific expression and recognition of self-antigen
Hepatitis resulting from liver-specific expression and recognition of self-antigen
复制标题
DOI：
10.1016/j.jaut.2008.04.015
复制
发表时间：
2008-11-01
影响因子：
12.8
通讯作者：
Peters, Marion G.
中科院分区：
文献类型：
--
作者：
Buxbaum, James;Qian, Peiqing;Peters, Marion G.
肝细胞表面抗原异常表达引起的肝脏特异性免疫反应性被认为是自身免疫性肝炎（AIH）发生的一个主要因素。当这些抗原没有被清除和/或反应没有得到适当的调节时，持续的炎症就会发生。我们培育了在肝细胞表面表达鸡卵白蛋白的转基因小鼠（OVA-HEP）。这些小鼠对卵清蛋白耐受，发育正常，在2岁之前没有肝脏或其他疾病的迹象。将初始卵清蛋白特异性T细胞过继转移到OVA-HEP转基因小鼠中，以剂量依赖的方式导致肝脏特异性炎症。这种肝坏死炎症依赖于CD8(+) V α 2 ova特异性T细胞，局限于肝脏，并在ova特异性CD4(+) T细胞的帮助下增强；但不是由卵清蛋白特异性CD4 T细胞过继性转移引起的。这种反应是自限性的，但在反复转移抗原特异性T细胞后，出现了持续的炎症。这种T细胞识别肝细胞抗原的模型可用于了解自身免疫性肝炎中免疫反应的许多肝脏特异性方面。(C) 2008 Elsevier Ltd版权所有。
Liver-specific immune reactivity in response to aberrant expression of antigen on the surface of hepatocytes is thought to be a major factor in development of autoimmune hepatitis (AIH). Persistent inflammation develops when these antigens are not eliminated and/or responses are not appropriately regulated. We have developed transgenic mice (OVA-HEP), which express chicken ovalbumin on the surface of hepatocytes. These mice are tolerant to ovalbumin, develop normally and have shown no evidence of liver or other disease up to 2 years of age. Adoptive transfer of naive ovalbumin-specific T cells into OVA-HEP transgenic mice led to liver-specific inflammation in a dose dependent manner. This hepatic necroinflammation was dependent upon CD8(+) V alpha 2 OVA-specific T cells, was limited to the liver, and was augmented by OVA-specific CD4(+) T cell help; but did not result from adoptive transfer of ovalbumin-specific CD4 T cells alone. The response was self-limited but persistent inflammation developed after repeated transfer of antigen-specific T cells. This model of T cell recognition of antigen on hepatocytes may be used to understand many liver-specific aspects of the immune response in autoimmune hepatitis. (C) 2008 Elsevier Ltd. All rights reserved.