Inhibition of T follicular helper cells mediated immune evasion in Japanese encephalitis virus infection (VIR1P.1146)

Japanese encephalitis virus (JEV) is a mosquito-borne neurotropic virus, which can escape from the peripheral immune response resulting in serious neuroinflammation. However, the mechanism of JEV immune evasion still remains unclear. In our study, it was found that both CD3+ and CD4+ T cell population dramatically decreased in the early stage of infection. And, T Follicular Helper Cell (TFH) counts reduced obviously accompanied with the decline of B cells, following the CD4+CD25+FoxP3+ regulatory T cells (Tregs) increased in the peripheral immune organs and blood after JEV infection. Co-inhibitory molecules CD279 (PD-1) and CD272 (BTLA) were upregulated on CD4+ T cells in JEV infected mouse, while CD274 (PD-1 ligand 1) was also upregulated on dendritic cells accordingly. IL-10, which indicating the immunosuppression, also dramatically increased in the whole process. Collectively, we hypothesis that there are two strategies involved in the JEV mediated immune evasion. On the one side, upregulation of the co-inhibitory molecules on T cells and APCs induces cell apoptosis of the CD3+ T cells, CD4+ T cells and TFH cells; on the other side, IL-10 may regulate TFH cells and Tregs differentiation. As a consequence, JEV evades from immune clearance and gains entry into the CNS leading to neuropathogenisis.