Interleukin-7 promotes CD8+ T cell activity in patients with enterovirus 71 associated encephalitis

Abstract

Enterovirus 71 (EV71) always induces severe hand, foot, and mouth disease with neurological complications, such as encephalitis. Interleukin (IL)-7 augments CD8+ T cells activity in chronic viral infection and cancers. However, few studies have focused on common γ-chain (γc) cytokine expression and regulatory function of IL-7 to CD8+ T cells in EV71 associated encephalitis. In this study, twenty-one patients with EV71 associated encephalitis, twenty-seven patients with febrile convulsion (FC), and twenty healthy individuals were enrolled. γc cytokine (IL-2, IL-4, IL-7 and IL-15) concentration was measured by ELISA. IL-7 receptor α chain (membrane/soluble CD127) expression was also investigated. Purified CD8+ T cells were stimulated with recombinant human IL-7 in vitro. The regulatory activity of IL-7 to CD8+ T cells from peripheral blood and cerebrospinal fluids (CSF) was investigated in direct and indirect contact co-culture with U-87MG cells. IL-7 in the serum and CSF, but not IL-2, IL-4, or IL-15, was significant increased in EV71 associated encephalitis. Both total CD127 mRNA relative level and membrane/soluble CD127 expression was comparable among three groups. IL-7 stimulation promoted CD8+ T cells proliferation, up-regulated perforin/granzyme B level, but reduced programmed death-1 expression in CD8+ T cells from EV71 associated encephalitis patients. Cytotoxicity and interferon-γ production of CD8+ T cells from peripheral blood and CSF was also augmented in response to IL-7 stimulation in both direct and indirect co-culture systems in EV71 associated encephalitis. The present data indicated that IL-7 induced cytolytic and non-cytolytic functions of CD8+ T cells in EV71 associated encephalitis. IL-7 might be considered as one of the immunomodulatory therapeutic candidates for EV71 infection.