CXCR6/CXCL16 is required for optimal NKT cell and dendritic cell interactions (33.2)

Abstract

Abstract Natural killer T (NKT) cells are a conserved T cell sublineage which rapidly produces cytokines upon activation by glycolipid antigens (i.e. α-GalCer) presented by dendritic cells (DC). Cross-talk between NKT cells and DCs is important in the initiation of anti-tumour responses. The objective of this study was to determine the role of CXCR6/CXCL16 in NKT cell-DC interactions. The chemokine receptor, CXCR6, is highly expressed on NKT cells, while its ligand, CXCL16, is expressed on DCs. When liver NKT cells were cultured with recombinant CXCL16 in vitro they were not activated directly. However, CXCL16 did enhance IFN-γ production in vitro when NKT cells were stimulated with suboptimal doses of plate bound anti-CD3. The presence of CXCL16 on the surface of DC is also important for NKT cell production of IFN-γ. NKT cells cultured with α-GalCer loaded CXCL16+ DC produced more IFN-γ than those cultured with CXCL16- DC. CXCL16+ DC stimulated more NKT cell IFN-γ production than CXCL16- DC in vivo as well. CD8+ DC constitutively express CXCL16 while all other DC subsets upregulate CXCL16 expression following α-GalCer stimulation. This is dependent on NKT cells since CXCL16 upregulation did not occur in NKT cell deficient (Jα18-/-) mice. DC maturation is also attenuated in the absence of CXCL16 signaling. These results suggest that CXCR6/CXCL16 is required for full NKT cell and dendritic cell activation/maturation.