Turtle, L;
Bali, T;
Buxton, G;
Chib, S;
Chan, S;
Soni, M;
Hussain, M;
... Solomon, T; + view all
(2016)
Human T cell responses to Japanese encephalitis virus in health and disease.
Journal of Experimental Medicine
, 213
(7)
pp. 1331-1352.
10.1084/jem.20151517.
Preview |
Text
1331.full.pdf - Published Version Download (3MB) | Preview |
Abstract
Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8+ and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4+ and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4+ T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4+ and CD8+ T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus.
| Type: | Article |
|---|---|
| Title: | Human T cell responses to Japanese encephalitis virus in health and disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1084/jem.20151517 |
| Publisher version: | https://doi.org/10.1084/jem.20151517 |
| Language: | English |
| Additional information: | This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org /terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial– Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10064137 |
Archive Staff Only
 |
View Item |
