The α-galactosylceramide KRN7000 was reported to be presented by CD1d to natural killer (NK) T cells, cells that are thought to play an important role in the rejection of malignant tumours and in the regulation of several autoimmune diseases. Here we analysed human peripheral blood (PB) NK T cells (Vα24+ Vβ11+ T cells) before and after a short-term culture in the presence of KRN7000. KRN7000 strongly activated PB Vα24+ Vβ11+ T cells and, when stimulated, the vast majority of these cells expressed interferon- γ (IFN-γ). Exposure of these KRN7000-cultured Vα24+ Vβ11+ T cells to interleukin-12 (IL-12), but not to IL-7, resulted in a relative increase in IFN-γ-expressing Vα24+ Vβ11+ T cells, compared with IL-4-expressing Vα24+ Vβ11+ T cells, indicating a shift towards a T-helper type 1 (Th1) phenotype. KRN7000 strongly up-regulated the expression of the cytotoxic molecule granzyme B (GrB) in Vα24+ Vβ11+ T cells. Although IL-7 resulted in a decrease in GrB levels in KRN7000-cultured Vα24+ Vβ11+ T cells, IL- 12 increased GrB levels in both Vα24+ Vβ11+ T cells and in Vα24+ Vβ11+ T-cell clones and increased cytotoxicity against hCD1d-transfected HeLa cells. Our data provide further insight into the characteristics of human Vα24+ Vβ11+ T cells and indicate that KRN7000 is a potent activator of Vα24+ Vβ11+ T cells. Combined with the established anti-tumour effects of KRN7000 in mouse models, these results may support the use of KRN7000 as an anti-tumour agent in man.
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