Department of Histology and Embryology, University of Rijeka, Rijeka, Croatia.
J Virol. 2012 Feb;86(4):2165-75. doi: 10.1128/JVI.06042-11. Epub 2011 Dec 7.
Natural killer (NK) cells and CD8(+) T cells play a prominent role in the clearance of mouse cytomegalovirus (MCMV) infection. The role of NK cells in modulating the CD8(+) T-cell response to MCMV infection is still the subject of intensive research. For analyzing the impact of NK cells on mounting of a CD8(+) T-cell response and the contribution of these cells to virus control during the first days postinfection (p.i.), we used C57BL/6 mice in which NK cells are specifically activated through the Ly49H receptor engaged by the MCMV-encoded ligand m157. Our results indicate that the requirement for CD8(+) T cells in early MCMV control inversely correlates with the engagement of Ly49H. While depletion of CD8(+) T cells has only a minor effect on the early control of wild-type MCMV, CD8(+) T cells are essential in the control of Δm157 virus. The frequencies of virus epitope-specific CD8(+) T cells and their activation status were higher in mice infected with Δm157 virus. In addition, these mice showed elevated levels of alpha interferon (IFN-α) and several other proinflammatory cytokines as early as 1.5 days p.i. Although the numbers of conventional dendritic cells (cDCs) were reduced later during infection, particularly in Δm157-infected mice, they were not significantly affected at the peak of the cytokine response. Altogether, we concluded that increased antigen load, preservation of early cDCs' function, and higher levels of innate cytokines collectively account for an enhanced CD8(+) T-cell response in C57BL/6 mice infected with a virus unable to activate NK cells via the Ly49H-m157 interaction.
自然杀伤 (NK) 细胞和 CD8(+) T 细胞在清除小鼠巨细胞病毒 (MCMV) 感染中发挥重要作用。NK 细胞在调节 CD8(+) T 细胞对 MCMV 感染反应中的作用仍然是深入研究的主题。为了分析 NK 细胞对 CD8(+) T 细胞反应的影响，以及这些细胞在感染后最初几天对病毒控制的贡献，我们使用了 C57BL/6 小鼠，其中 NK 细胞通过 Ly49H 受体特异性激活，该受体被 MCMV 编码的配体 m157 结合。我们的结果表明，CD8(+) T 细胞在早期 MCMV 控制中的需求与 Ly49H 的结合呈负相关。虽然耗尽 CD8(+) T 细胞对野生型 MCMV 的早期控制只有很小的影响，但 CD8(+) T 细胞在控制 Δm157 病毒中是必不可少的。感染 Δm157 病毒的小鼠中病毒表位特异性 CD8(+) T 细胞的频率及其激活状态更高。此外，这些小鼠在感染后 1.5 天就表现出更高水平的α干扰素 (IFN-α) 和其他几种促炎细胞因子。尽管在感染过程中晚期常规树突状细胞 (cDC) 的数量减少，特别是在感染 Δm157 的小鼠中，但在细胞因子反应的高峰期它们并没有受到显著影响。总的来说，我们得出的结论是，抗原负荷增加、早期 cDC 功能的保留以及先天细胞因子水平的升高共同导致感染无法通过 Ly49H-m157 相互作用激活 NK 细胞的 C57BL/6 小鼠中 CD8(+) T 细胞反应增强。
