Institute of Microbiology, Department of Biology, ETH Zürich, Zürich, Switzerland.
Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
Immun Inflamm Dis. 2020 Sep;8(3):249-257. doi: 10.1002/iid3.300. Epub 2020 Mar 26.
Epidemiological data suggest that persistent viral infections impair immune homeostasis and immune responsiveness. Previous studies showed that chronic virus infections negatively impact bystander T-cell differentiation and memory formation but there is limited knowledge of how chronic virus infections impinge on heterologous naive T-cell populations.
We used adoptive transfer of naive CD8 T cells with defined nonviral specificity into hosts, which were subsequently chronically infected with lymphocytic choriomeningitis virus, followed by analyses of numeric, phenotypic, and functional changes provoked in the chronically infected host.
We demonstrate that chronic virus infections have a profound effect on the number and phenotype of naive bystander CD8 T cells. Moreover, primary expansion upon antigen encounter was severely compromised in chronically infected hosts. However, when naive bystander CD8 T cells were transferred from the chronically infected mice into naive hosts, they regained their expansion potential. Conversely, when chronically infected hosts were supplied with additional antigen-presenting cells (APCs), primary expansion of the naive CD8 T cells was restored to levels of the uninfected hosts.
Our results document numeric, phenotypic, and functional adaptation of bystander naive CD8 T cells during nonrelated chronic viral infection. Their functional impairment was only evident in the chronically infected host, indicating that T-cell extrinsic factors, in particular the quality of priming APCs, are responsible for the impaired function of naive bystander T cells in the chronically infected hosts.
流行病学数据表明，持续性病毒感染会损害免疫稳态和免疫应答。先前的研究表明，慢性病毒感染会对旁观者 T 细胞分化和记忆形成产生负面影响，但对于慢性病毒感染如何影响异源初始 T 细胞群体知之甚少。
我们通过将具有明确非病毒特异性的初始 CD8 T 细胞过继转移到随后被淋巴细胞性脉络丛脑膜炎病毒慢性感染的宿主中，然后分析慢性感染宿主中引发的数量、表型和功能变化。
我们证明慢性病毒感染对初始旁观者 CD8 T 细胞的数量和表型有深远影响。此外，在慢性感染的宿主中，抗原初次扩增受到严重损害。然而，当初始旁观者 CD8 T 细胞从慢性感染的小鼠转移到初始宿主中时，它们恢复了扩增潜能。相反，当慢性感染的宿主提供额外的抗原呈递细胞（APCs）时，初始 CD8 T 细胞的扩增恢复到未感染宿主的水平。
我们的结果记录了非相关慢性病毒感染期间旁观者初始 CD8 T 细胞的数量、表型和功能适应性。它们的功能障碍仅在慢性感染的宿主中显现，表明 T 细胞外在因素，特别是初始 APC 的质量，是导致慢性感染宿主中初始旁观者 T 细胞功能受损的原因。
