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


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.


CONCLUSIONS
TLR agonists may act as strong adjuvants for immunotherapy by promoting combined and reciprocal activation of iNKT cells and DCs.
Moreno
María
M
VU University Medical Center, The Netherlands.
Mol
Berber M
BM
von Mensdorff-Pouilly
Silvia
S
Verheijen
René H M
RH
de Jong
Esther C
EC
von Blomberg
B Mary E
BM
van den Eertwegh
Alfons J M
AJ
Scheper
Rik J
RJ
Bontkes
Hetty J
HJ
D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005408:Flagellin / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010457:Peptidoglycan / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000819:agonists
C551788:CL 075; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D010457:Peptidoglycan; D011804:Quinolines; D013844:Thiazoles; D051193:Toll-Like Receptors; D005408:Flagellin; D007371:Interferon-gamma; D011070:Poly I-C