Belz G T, Altman J D, Doherty P C
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13812-7. doi: 10.1073/pnas.95.23.13812.
Dissection of the primary and secondary response to an influenza A virus established that the liver contains a substantial population of CD8(+) T cells specific for the immunodominant epitope formed by H-2Db and the influenza virus nucleoprotein peptide fragment NP366-374 (DbNP366). The numbers of CD8(+) DbNP366(+) cells in the liver reflected the magnitude of the inflammatory process in the pneumonic lung, though replication of this influenza virus is limited to the respiratory tract. Analysis of surface phenotypes indicated that the liver CD8(+) DbNP366(+) cells tended to be more "activated" than the set recovered from lymphoid tissue but generally less so than those from the lung. The distinguishing characteristic of the lymphocytes from the liver was that the prevalence of the CD8(+) DbNP366(+) set was always much higher than the percentage of CD8(+) T cells that could be induced to synthesize interferon gamma after short-term, in vitro stimulation with the NP366-374 peptide, whereas these values were generally comparable for virus-specific CD8(+) T cells recovered from other tissue sites. Also, the numbers of apoptotic CD8(+) T cells were higher in the liver. The results overall are consistent with the idea that antigen-specific CD8(+) T cells are destroyed in the liver during the control and resolution phases of this viral infection, though this destruction is not necessarily an immediate process.
对甲型流感病毒的初次和二次反应进行剖析后发现，肝脏中含有大量针对由H-2Db和流感病毒核蛋白肽片段NP366-374（DbNP366）形成的免疫显性表位的CD8(+) T细胞。尽管这种流感病毒的复制仅限于呼吸道，但肝脏中CD8(+) DbNP366(+)细胞的数量反映了肺炎肺中炎症过程的程度。表面表型分析表明，肝脏中的CD8(+) DbNP366(+)细胞往往比从淋巴组织中回收的细胞更“活化”，但一般比从肺中回收的细胞活化程度低。来自肝脏的淋巴细胞的显著特征是，CD8(+) DbNP366(+)细胞群的比例总是远高于用NP366-374肽进行短期体外刺激后可诱导合成干扰素γ的CD8(+) T细胞的百分比，而对于从其他组织部位回收的病毒特异性CD8(+) T细胞，这些值通常是相当的。此外，肝脏中凋亡的CD8(+) T细胞数量更多。总体结果与以下观点一致，即在这种病毒感染的控制和消退阶段，抗原特异性CD8(+) T细胞在肝脏中被破坏，尽管这种破坏不一定是一个即时过程。
