AUTHOR=Zhang Xiyue , Zhang Yusi , Liu He , Tang Kang , Zhang Chunmei , Wang Meng , Xue Manling , Jia Xiaozhou , Hu Haifeng , Li Na , Zhuang Ran , Jin Boquan , Zhang Fanglin , Zhang Yun , Ma Ying 

TITLE=IL-15 induced bystander activation of CD8+ T cells may mediate endothelium injury through NKG2D in Hantaan virus infection

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.1084841

DOI=10.3389/fcimb.2022.1084841

ISSN=2235-2988

ABSTRACT=Hantaan virus (HTNV) can cause lethal hemorrhagic fever with renal syndrome (HFRS) in human and is characterized by increased vascular permeability, which is correlated with the endothelium injury in HFRS patients. Many studies have shown that bystander activation of CD8+ T cells by virus infection may be involved in host injury. However, the role of bystander-activated CD8+ T cell responses in HTNV infection is unclear. Here we showed that there were bystander activation of CD8+ T cells after HTNV infection by detecting activated EBV or CMV-specific CD8+ T cells in HFRS patients. HTNV-infected human umbilical vein endothelial cells (HUVECs) in vitro could produce high levels of interleukin-15 (IL-15), which was positively correlated with disease severity and the expression of NKG2D on bystander-activated CD8+ T cells. Moreover, the elevated IL-15 could induce activation of CD122 (IL-15Rβ)+NKG2D+ EBV/CMV-specific CD8+ T cells. Meanwhile, the expression of IL-15Rα and ligand for NKG2D were upregulated on HTNV-infected HUVECs. Importantly, bystander-activated CD8+ T cells could exert cytotoxicity effects against HTNV-infected HUVECs, which could be enhanced by IL-15 stimulation and blocked by NKG2D antibody. Taking together, IL-15 induced bystander activation of CD8+ T cells may mediate endothelium injury through NKG2D during HTNV infection.