Dong Haidong, Zhu Gefeng, Tamada Koji, Flies Dallas B, van Deursen Jan M A, Chen Lieping
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Immunity. 2004 Mar;20(3):327-36. doi: 10.1016/s1074-7613(04)00050-0.
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.
在被抗原全身激活后，CD8(+)而非CD4(+) T细胞在肝脏中选择性聚集并发生凋亡，这一机制与肝脏耐受性的诱导及慢性感染相关。在此过程中CD8(+) T细胞偏好的分子基础尚不清楚。我们通过基因靶向制备了B7-H1缺陷小鼠，发现肝脏中CD8(+) T细胞自发聚集，而CD4(+) T细胞水平保持正常。此外，抗原驱动的CD8(+) T细胞正常增殖，而在收缩期肝脏中的凋亡水平选择性受损，导致实验性自身免疫性肝炎中肝细胞损伤加速。因此，B7-H1是一种关键蛋白，可选择性调节肝内CD8(+) T细胞的聚集和清除，也可能在肝脏炎症、自身免疫性疾病及耐受性中发挥作用。
