Shytikov Dmytro, Rohila Deepak, Li Dan, Wang Pengfei, Jiang Mei, Zhang Mingxu, Xu Qin, Lu Linrong
Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou, China.
Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, China.
Front Immunol. 2021 Jan 7;11:602783. doi: 10.3389/fimmu.2020.602783. eCollection 2020.
The role of Ly49CD8 T-cells in the immune system is not clear. Previously, several papers suggested Ly49CD8 T-cells as immunosuppressors, while multiple studies also suggested their role as potent participants of the immune response. The mechanism of Ly49 expression on CD8 T-cells is also not clear. We investigated phenotype, functions, and regulation of Ly49 expression on murine CD8 T-cells in both normal state and during LCMV infection. CD8 T-cells express different Ly49 receptors compared with NK-cells. In intact mice, Ly49CD8 T-cells have a phenotype similar to resting central memory CD8 T-cells and do not show impaired proliferation and cytokine production. Conventional CD8 T-cells upregulate Ly49 receptors during TCR-induced stimulation, and IL-2, as well as IL-15, affect it. At the same time, Ly49CD8 T-cells change the Ly49 expression profile dramatically upon re-stimulation downregulating inhibitory and upregulating activating Ly49 receptors. We observed the expression of Ly49 receptors on the virus-specific CD8 T-cells during LCMV infection, especially marked in the early stages, and participation of Ly49CD8 T-cells in the anti-viral response. Thus, CD8 T-cells acquire Ly49 receptors during the T-cell activation and show dynamic regulation of Ly49 receptors during stimulation.
Ly49CD8 T细胞在免疫系统中的作用尚不清楚。此前,有几篇论文认为Ly49CD8 T细胞是免疫抑制细胞,而多项研究也表明它们是免疫反应的有力参与者。CD8 T细胞上Ly49表达的机制也不清楚。我们研究了正常状态和LCMV感染期间小鼠CD8 T细胞上Ly49表达的表型、功能和调控。与自然杀伤细胞相比,CD8 T细胞表达不同的Ly49受体。在完整小鼠中,Ly49CD8 T细胞具有类似于静息中央记忆CD8 T细胞的表型,并且未显示出增殖和细胞因子产生受损。传统CD8 T细胞在TCR诱导的刺激过程中上调Ly49受体,白细胞介素-2以及白细胞介素-15会对其产生影响。同时,Ly49CD8 T细胞在再次刺激时会显著改变Ly49表达谱,下调抑制性Ly49受体并上调激活性Ly49受体。我们观察到LCMV感染期间病毒特异性CD8 T细胞上Ly49受体的表达,在早期尤为明显,并且Ly49CD8 T细胞参与了抗病毒反应。因此,CD8 T细胞在T细胞活化过程中获得Ly49受体,并在刺激过程中表现出Ly49受体的动态调控。