Type I IFN-mediated enhancement of anti-leukemic cytotoxicity of γδ T cells expanded from peripheral blood cells by stimulation with zoledronate

BackgroundIn order to establish efficient γδ T-cell based tumor immunotherapy, we explored a method to enhance the cytotoxicity of γδ T cells against leukemia cells by stimulating γδ T cells with type I IFN.Methodsγδ T cells were expanded from normal PBMC by culturing with zoledronate and a low concentration of IL-2 for 2 weeks. For the activation of γδ T cells, γδ T cells were cultured with type I IFN (HLBI, IFN-α2b and IFN-β) for 1–3 days. The cytotoxicity of HLBI-activated γδ T cells against leukemia cell lines and fresh leukemia cells was evaluated by 51Cr-release assay.Resultsγδ T cells, which were expanded and purified with magnetic beads using an anti-γδ TCR MAb, were demonstrated to be cytotoxic against leukemia cell lines of both lymphoid and myeloid origin and fresh myeloid leukemia cells. By culturing expanded γδ T cells with type I IFN, the expression of the activation marker CD69 was increased and the cytometric bead array showed an elevated production of IFN-γ by γδ T cells. In addition, the cytotoxicity of γδ T cells against leukemia cells was definitely enhanced by culturing γδ T cells with HLBI.DiscussionThe present study has demonstrated that type I IFN could enhance the anti-leukemic cytotoxicity of expanded γδ T cells, which implies that in vitro bisphosphonate (such as zoledronate)-expanded and type I IFN-activated γδ T cells could be applied to immunotherapy for hematologic malignancies such as leukemia and lymphoma.