Cd8~+ T Cells Immune Response During Japanese Encephalitis Virus Infection

Japanese encephalitis virus(JEV),which is a mosquito-borne member of the genus Flavivirus,is responsible for most acute and epidemic cases of viral encephalitis.Approximately 60%of the world's population inhabits JEV endemic areas,and the virus is continuing to spread in the previously unaffected regions due to global warming.The majority of the virus can be cleared by the immune system of the host during JEV infection,but a little amount of virus can escape from the immune response,cross the blood-brain barrier(BBB)and enter the central nervous system(CNS).In this study,we investigated the mechanism of how JEV escape the adaptive immune response.Firstly,six or eight-week-old age-matched C57BL/6 mice were intravenously infected with JEV.The expression of MHC class?antigen processing related genes were first measured in the spleen by RT-PCR,flow cytometry was then used to measure the expression of MHC class?on the dendritic cells and macrophage in the spleen,and to detect the MHC class?antigen processing related genes obtained from the bone marrow-derived macrophage.The results showed that the expression of MHC class?antigen processing related genes were decreased in spleen.The expression of MHC class?was upregulated on dendritic cells and macrophage.Meanwhile,the expression of MHC class?antigen processing related genes on bone marrow-derived macrophage were also increased,which may contribute to the activation of CD8~+T cells.Secondly,we detected the expression of costimulatory molecules on dendritic cells,macrophage and CD8~+T cells by flow cytometry.The results showed that the expression of co-activated molecules was upregulated on dendritic cells,macrophage and CD8~+T cells,along with the upregulation of co-inhibited molecules,which may influence CD8~+T cells activation.Finally,the expression of effector molecules on CD8~+T cells was detected which isolated from lymph node of JEV P3-infected mice by flow cytometry.And the proportion of CD8~+T cells in the spleen of JEV-infected mice was also determined by flow cytometry.Meanwhile,the cytotoxicity of CD8~+T cells to kill target cells was determined by killing assay in vitro.The results indicated that JEV P3 mediates the activation of CD8~+T cells and enhances their effector function,but the proportion of CD8~+T cells was significantly decreased,which may also affects outcome of the immune response individually.In summary,JEV P3 mediates the activation of CD8~+T cells and enhances their killing function,but reduces the proportion of CD8~+T cells significantly,which may affect the cellular immune response on the individual level and mediate the escape of the virus.This study enhances a better understanding of JEV immune escape mechanism during infection and it provides a reference for related researches.