Liu Z X, Govindarajan S, Okamoto S, Dennert G
Department of Molecular Microbiology and Immunology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine at University of Southern California, Los Angeles, CA 90089, USA.
J Immunol. 2001 Mar 1;166(5):3035-41. doi: 10.4049/jimmunol.166.5.3035.
Immunity to allogeneic MHC Ags is weak in rodent livers, raising questions as to the mechanisms that might control responses in this organ. Infection with an adenovirus vector reveals that T cell-mediated immunity to nonself-Ags in the liver is self-limiting. Virus-induced liver injury decreases and coincides with disappearance of virus-specific CTL, concomitant to an increase of apoptotic T cells early after infection. But whereas death in CD4 cells is independent of Fas, perforin, and TNF-alpha, that of CD8 cells requires Fas and not perforin or TNF-alpha pathways. Fas ligand is expressed on liver-infiltrating cells, pointing to death by fratricide that causes almost complete disappearance of virus-specific CTL 4 wk after infection. CTL elimination is virus dose dependent, and high doses induced high alanine aminotransferase values, elevated expression of Fas ligand on CD8 cells, and increased CD8 cell migration into the infected liver.
啮齿动物肝脏对同种异体MHC抗原的免疫反应较弱，这引发了关于可能控制该器官免疫反应机制的问题。腺病毒载体感染显示，肝脏中T细胞介导的对非自身抗原的免疫反应是自我限制的。病毒诱导的肝损伤减轻，并与病毒特异性CTL的消失同时发生，同时在感染后早期凋亡T细胞增加。但是，虽然CD4细胞的死亡与Fas、穿孔素和TNF-α无关，但CD8细胞的死亡需要Fas，而不是穿孔素或TNF-α途径。Fas配体在肝浸润细胞上表达，表明通过自相残杀导致死亡，这使得感染后4周病毒特异性CTL几乎完全消失。CTL的清除是病毒剂量依赖性的，高剂量会导致高丙氨酸转氨酶值、CD8细胞上Fas配体表达升高以及CD8细胞向感染肝脏的迁移增加。
