Human T cell responses to Japanese encephalitis virus in health and disease

Lance Turtle, et al., Journal of Experimental Medicine. 2016. 213:1331-52.

Speaker: Wan-Yu Wang (王琬瑜)                         Time: 15:00~16:00, Nov 09, 2016

Commentator: Dr. Ai-Li Shiau (蕭璦莉 老師)    Place: Room 601

Abstract:

Japanese encephalitis virus (JEV) is the main cause of viral encephalitis in children of South and Southeast Asia with an estimated 68,000 cases annually. However, most infected people develop mild or no symptoms at all. Protection by neutralizing antibodies to JEV is well-known; in contrast, cell-mediated immunity to JEV is less studied. In addition, some studies show that JEV cocirculates with other flaviviruses in endemic areas, notably the dengue virus (DENV), and suggest cross-protection between DENV and JEV ^{[1, 2]}. To investigate the role of T cell responses in the protection against JEV, the authors used a full-length synthetic peptide library to analyze the extent of the human T cell responses ex vivo. In healthy JEV-exposed donors, polyfunctional and cytotoxic phenotypes were dominated by CD8⁺ T cell response also showing highly flavivirus cross-reactivity. While in convalescent JE patients, JEV-specific CD4⁺ T cells show IFN-g-dominant response with a good quality correlated with better clinical outcome. IFN-γ responses in healthy JEV-exposed donors were mostly induced by nonstructural (NS) protein 3 and NS5, whereas recovered JE patients responded to all JEV proteins with slightly increase against the C/prM and NS1/NS2. Furthermore, T cells of convalescent JE patients targeted specific JEV-region which is less conserved among flavivirus. Besides, highly cross-reactive T cell responses are induced in healthy JEV-exposed donors. These data show the diverse functions and targets of CD4⁺ and CD8⁺ T cell responses relate to different clinical outcomes of JEV infection. Based on these results, the good outcome of cross-reactive T cell responses provides the potential strategy for vaccine targeting.

References:

1.         Libraty, D.H., et al. Clinical and immunological risk factors for severe disease in Japanese encephalitis. Trans. R. Soc. Trop. Med. Hyg. 2002. 96, 173–178.

2.         Hoke, C.H.A., et al. Protection against Japanese encephalitis by inactivated vaccines. N. Engl. J. Med. 1988. 319, 608–614.