TY - JOUR
T1 - Differential indirect activation of human invariant natural killer T cells by Toll-like receptor agonists
AU - Moreno, María
AU - Mol, Berber M.
AU - von Mensdorff-Pouilly, Silvia
AU - Verheijen, René H. M.
AU - de Jong, Esther C.
AU - von Blomberg, B. Mary E.
AU - van den Eertwegh, Alfons J. M.
AU - Scheper, Rik J.
AU - Bontkes, Hetty J.
AU - von Blomberg-van der Flier, B.M.E.
PY - 2009
Y1 - 2009
N2 - 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 reciprocal activation of iNKT cells and DCs
AB - 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 reciprocal activation of iNKT cells and DCs
U2 - https://doi.org/10.2217/IMT.09.30
DO - https://doi.org/10.2217/IMT.09.30
M3 - Article
C2 - 20635987
SN - 1750-743X
VL - 1
SP - 557
EP - 570
JO - Immunotherapy
JF - Immunotherapy
IS - 4
ER -