Japanese encephalitis virus produces a CD4+ Th2 response and associated immunoprotection in an adoptive-transfer...

Japanese encephalitis is an acute infection of the central nervous system caused by Japanese encephalitis virus (JEV). The importance of an effective humoral response in preventing JEV infection has already been established, although the contribution of cellular immunity remains unclear. This study used an experimental murine model to understand the protective effects of cell-mediated immunity in JEV infection. Fourteen-day-old mice adoptively transferred with JEV-immune splenocytes were found to be protected from peripheral JEV challenge. The survival rate was reduced when transferred cells were depleted of their CD4(+) T-cell population. Correspondingly, increased protection was observed when JEV-primed isolated CD4(+) T cells were transferred compared with isolated CD8(+) T cells. Mice protected from JEV infection by the adoptive transfer of JEV-immune splenocytes had higher levels of immunomodulatory cytokines and decreased expression of pro-inflammatory cytokines. Concurrent with the increase in Th2 cytokines, JEV-specific IgM and IgG1 antibody titres were found to be elevated in protected mice. Taken together, these data indicate a definite role for CD4(+) T cells in protection from lethal JEV infection in naïve 14-day-old mice. Induction of a Th2 cytokine response and IgG1 antibody probably achieves an immunomodulatory effect that results in the enhanced survival of these animals.