Differential indirect activation of human invariant natural killer T cells by Toll-like receptor agonists.

Aim: Invariant natural killer (iNK) T cells are activated by bacterial glycosphingolipids presented by CD1d on dendritic cells (DCs). Here, it was investigated whether Toll-like receptor (TLR) ligands derived from various microorganisms can either directly or indirectly (through DC activation) activate iNKT cells. Materials & Methods: TLR expression by iNKT cells was examined and the ability of various TLR ligands to activate iNKT cells was evaluated. Results: Although human iNKT cells express all TLRs, apart from TLR8, they did not respond directly to TLR ligands. However, iNKT cells became strongly activated when total peripheral blood mononuclear cells were stimulated with TLR2/6, 7/8 and 9 ligands, but not or to a lesser extent with TLR3, 4 and 5 ligands. TLR-stimulated monocyte-derived DCs promoted iNKT cell phenotypic activation and, in turn, these activated iNKT cells further enhanced DC maturation. Conclusion: TLR agonists may act as strong adjuvants for immunotherapy by promoting combined and rec...