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

dc.contributor.authorLance Turtleen_US
dc.contributor.authorTanushka Balien_US
dc.contributor.authorGemma Buxtonen_US
dc.contributor.authorSavita Chiben_US
dc.contributor.authorSajesh Chanen_US
dc.contributor.authorMohammed Sonien_US
dc.contributor.authorMohammed Hussainen_US
dc.contributor.authorHeather Isenmanen_US
dc.contributor.authorPrachi Fadnisen_US
dc.contributor.authorManjunatha M. Venkataswamyen_US
dc.contributor.authorVishali Satishkumaren_US
dc.contributor.authorPenny Lewthwaiteen_US
dc.contributor.authorAyako Kuriokaen_US
dc.contributor.authorSrinivasa Krishnaen_US
dc.contributor.authorM. Veera Shankaren_US
dc.contributor.authorRiyaz Ahmeden_US
dc.contributor.authorAshia Begumen_US
dc.contributor.authorVasanthapuram Ravien_US
dc.contributor.authorAnita Desaien_US
dc.contributor.authorSutee Yoksanen_US
dc.contributor.authorStefan Fernandezen_US
dc.contributor.authorChristian B. Willbergen_US
dc.contributor.authorHenrik N. Kloverprisen_US
dc.contributor.authorChristopher Conlonen_US
dc.contributor.authorPaul Klenermanen_US
dc.contributor.authorVijaya Satchidanandamen_US
dc.contributor.authorTom Solomonen_US
dc.contributor.otherUniversity of Liverpoolen_US
dc.contributor.otherRoyal Liverpool and Broadgreen University Hospitals NHS Trusten_US
dc.contributor.otherIndian Institute of Science, Bangaloreen_US
dc.contributor.otherVijayanagar Institute of Medical Sciencesen_US
dc.contributor.otherNational Institute of Mental Health and Neuro Sciencesen_US
dc.contributor.otherNational Health Serviceen_US
dc.contributor.otherUniversity of Oxforden_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherArmed Forces Research Institute of Medical Sciences, Thailanden_US
dc.description.abstract© 2016 Turtle et al. 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.en_US
dc.identifier.citationJournal of Experimental Medicine. Vol.213, No.7 (2016), 1331-1352en_US
dc.rightsMahidol Universityen_US
dc.subjectImmunology and Microbiologyen_US
dc.titleHuman T cell responses to Japanese encephalitis virus in health and diseaseen_US