Human Vγ9Vδ2-T cells exhibit potent antiviral activity against EV71 infection

Abstract

Enterovirus 71 (EV71) is a major pathogen of hand, foot and mouth disease (HFMD). It is highly contagious and usually causes mild disease. However, occasionlly HFMD caused by EV71 would develpoed into severe neurological complications or even deaths in young children. There is no effective anti-viral therapy against EV71 infection. Human Vγ9Vδ2-T cells, as the first line of human immune defense, exhibit antiviral activities against different viruses. However, whether human Vγ9Vδ2-T cells have antiviral activity against EV71 remains unkown. In this study, we used EV71-infected primary human monocyte-derived macrophages (MDMs) to examine the anti-EV71 activity of Vγ9Vδ2-T cells. We found that phosphoantigen pamidronate-expanded Vγ9Vδ2-T cells could kill EV71-infected MDMs, and thus reduce the viral load. The cytotoxicity of Vγ9Vδ2-T cells against EV71-infected MDMs required cell-cell contact and mediated by Fas/FasL pathway. Vγ9Vδ2-T cells also displayed potent capacity to produce IFN-γ and thus inhibit EV71 viral replication. CCR5 pathway was involved in the migration of Vγ9Vδ2 T cells towards EV71-infected cells. These results demonstrated that Vγ9Vδ2-T cells have both cytotoxic and non-cytolytic antiviral activities target EV71. Our data suggests a novel therapeutic approach against EV71 by boosting Vγ9Vδ2 T cell immunity.