Characteristics of virus-specific CD8+ T cells in the liver during the control and resolution phases of influenza pneumonia
Characteristics of virus-specific CD8+ T cells in the liver during the control and resolution phases of influenza pneumonia
复制标题
DOI：
10.1073/pnas.95.23.13812
复制
发表时间：
1998-11-10
影响因子：
11.1
通讯作者：
Doherty, PC
中科院分区：
文献类型：
--
作者：
Belz, GT;Altman, JD;Doherty, PC
对甲型流感病毒的初级和次级反应的剖析表明，肝脏含有大量对 H-2D(b) 和流感病毒核蛋白肽片段 NP366-374 (DbNP366) 形成的免疫显性表位具有特异性的 CD8(+) T 细胞。肝脏中 CD8(+) DbNP366(+) 细胞的数量反映了肺炎肺部炎症过程的严重程度，尽管这种流感病毒的复制仅限于呼吸道。表面表型分析表明，肝脏CD8(+) DbNP366(+)细胞往往比从淋巴组织中回收的细胞更“活化”，但通常不如肺中的细胞“活化”。来自肝脏的淋巴细胞的显着特征是，CD8(+) DbNP366(+)组的流行率始终远高于在用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，而这些值通常与从其他组织部位回收的病毒特异性CD8(+) T细胞相当。此外，肝脏中凋亡的CD8(+) T细胞数量也较高。总体而言，结果与抗原特异性 CD8+ T 细胞在病毒感染的控制和消退阶段在肝脏中被破坏的观点一致，尽管这种破坏不一定是立即的过程。
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-2D(b) 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.