Impaired T helper 1 function of nonstructural protein 3-specific T cells in Japanese patients with encephalitis with neurological sequelae

Japanese encephalitis virus (JEV) is the principal cause of viral encephalitis. The predominance of children among patients with encephalitis in areas where JEV is endemic that do not have immunization programs suggests that acquired immunity is critical in protecting adults against symptomatic JEV encephalitis. We characterized and compared the T cell response to nonstructural (NS) protein 3 between healthy individuals naturally exposed to JEV and patients in the convalescent phase of JEV encephalitis. The NS3 protein, used as a fusion to the 11-amino acid protein transduction domain of human immunodeficiency virus Tat, elicited CD4(+) and T helper-dependent CD8(+) T cell responses. The production of interferon (IFN)-gamma by responding T cells was significantly higher in healthy donors than in patients, correlating strongly with acquired protective immunity to JEV. Furthermore, a striking inverse association between IFN-gamma levels and the severity of postencephalitic sequelae in patients implicated a role of IFN-gamma in recovery.