B7-H1 determines accumulation and deletion of intrahepatic CD8+ T lymphocytes
B7-H1 determines accumulation and deletion of intrahepatic CD8+ T lymphocytes
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DOI：
10.1016/s1074-7613(04)00050-0
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发表时间：
2004-03-01
期刊：
影响因子：
32.4
通讯作者：
Chen, LP
中科院分区：
文献类型：
--
作者：
Dong, HD;Zhu, GF;Chen, LP
在被抗原CD 8（+）而不是CD 4（+）全身激活后，T细胞选择性地在肝脏中积聚并经历凋亡，这是与诱导肝耐受和慢性感染相关的机制。在这个过程中，CD 8（+）T细胞偏好的分子基础是未知的。我们通过基因靶向制备了B7-H1缺陷小鼠，发现肝脏中CD 8（+）T细胞自发聚集，而CD 4（+）T细胞水平保持正常。此外，抗原驱动的CD 8（+）T细胞正常增殖，而在收缩期的凋亡水平在肝脏中选择性受损，导致实验性自身免疫性肝炎肝细胞损伤加速。因此，B7-H1是选择性调节肝内CD 8（+）T细胞积累和缺失的关键蛋白，也可能导致炎症，自身免疫性疾病和肝脏耐受。
Upon systemic activation by antigens, CD8(+), but not CD4(+), T cells selectively accumulate and undergo apoptosis in the liver, a mechanism associated with the induction of hepatic tolerance and chronic infection. The molecular basis for CD8(+) T cell preference in this process is unknown. We prepared B7-H1-deficient mice by gene targeting and found spontaneous accumulation of CD8(+) T cells in the liver while CD4(+) T cell levels remained normal. Moreover, antigen-driven CD8(+) T cells proliferated normally while apoptotic levels during the contraction phase was selectively impaired in the liver, leading to accelerated hepatocyte damage in experimental autoimmune hepatitis. Therefore, B7-H1 is a key protein selectively regulating the accumulation and deletion of intrahepatic CD8(+) T cells and may also contribute to inflammation, autoimmune diseases, and tolerance in the liver.