Polarization of Vα24⁺ Vβ11⁺ natural killer T cells of healthy volunteers and cancer patients using α-galactosylceramide-loaded and environmentally instructed dendritic cells

CD1d-restricted natural killer T (NKT) cells play important regulatory roles in various immune responses. NKT cell-derived T helper (Th) 1 cytokines are important in the induction of antitumor immune responses in mice. Because the CD1d-restricted Vα24⁺ Vβ11⁺ NKT cell population in cancer patients is decreased both in size and in its capacity to secrete IFN-γ, therapeutic strategies based on reconstitution of type 1 polarized Vα24⁺ Vβ11⁺ NKT cells merit additional investigation. Here, we report the simultaneous strong expansion and type 1 polarization of human invariant Vα24⁺ Vβ11⁺ NKT cells using α-galactosylceramide-loaded type 1 dendritic cells and interleukin 15. Type 1 polarized Vα24⁺ Vβ11⁺ NKT cells produced high levels of IFN-γ, tumor necrosis factor α, and granulocyte macrophage colony-stimulating factor, and induced strong cytotoxicity in Jurkat cells in an α-galactosylceramide-dependent manner. Importantly, the cytokine profile of Vα24⁺ Vβ11⁺ NKT cells that were initially expanded under Th2 polarizing conditions could be reversed to a Thl cytokine profile, indicating the plasticity of the cytokine profile of the human adult Vα24⁺ Vβ11⁺ NKT cell population.