The antiviral and antitumor characteristics of human gammadelta-T cells

Abstract

γδ-T cells represent for a small population of immune cells, but play indispensible role in host defense against exogenous pathogen, immune surveillance on endogenous pathogenesis and even homeostasis of immune system. The activation and expansion of γδ-T cells are generally observed in diverse human diseases and correlate with the progress and prognosis of diseases. γδ-T cells have both “innate” and “adaptive” like characteristics in immune responses, and their antiviral and antitumor activities can be carried out by multiple pathways that are under elaborate regulation by other immune components. Recently, we found that human Vγ9Vδ2-T cells expanded by the aminobisphosphonate pamidronate can kill influenza virus-infected cells and inhibit the replication of various influenza viruses, including human and avian seasonal and pandemic influenza viruses. The cytotoxicity of Vγ9Vδ2-T cells against influenza virusinfected cells was dependent on NKG2D activation, and mediated by Fas-FasL and perforin-granzyme B pathways. More recently, we also showed that pamidronateexpanded human Vγ9Vδ2-T cells can efficiently kill EBV-transformed autologous lymphoblastoid B cell tumor lines through γδ-TCR and NKG2D receptor triggering, and Fas and TRAIL engagement. Using humanized mouse model, we further demonstrated that targeted activation of human Vγ9Vδ2-T cells can control influenza diseases and EBV-induced lymphoproliferative disease by using pamidronate to selectively enhance human γδ-T cell immunity. As pamidronate has been already used for decades in osteoporosis treatment, this ‘new application of an old drug’ potentially offers a safe and readily available option for the treatment of influenza virus infection and EBV-induced tumors.