Costimulatory activation of murine invariant natural killer T cells by toll-like receptor agonists.
Invariant NKT (iNKT) cells are glycolipid-reactive lymphocytes with anti-microbial properties. Toll-like receptor (TLR)-primed antigen-presenting cells are known to activate iNKT cells, however, the expression and function of TLRs in iNKT cells remain largely unknown. Here, we show that TCR-activation of murine iNKT cells by α-GalactosylCeramide (α-GalCer) or anti-CD3 antibodies can result in increased expression of TLR genes. TLR3, 5 and 9-mediated costimulation of TCR-preactivated iNKT cells resulted in enhancement of iNKT cell activation, as determined by their cytokine production. Expression of TLR3 and 9 at protein level was also confirmed in TCR-activated iNKT cells. Furthermore, TCR-preactivation followed by TLR9-costimulation of iNKT cells increased their ability to induce maturation of dendritic cells. Thus, our findings show that iNKT cells can up-regulate their TLR expression upon TCR activation and a subsequent TLR-signaling in these cells can lead to their enhanced activation, suggesting a new possible mode of iNKT cell activation.
Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
Raveendra R
RR
Kulkarni
Alexander Ian
AI
Villanueva
Inas
I
Elawadli
Preethi
P
Jayanth
Leah R
LR
Read
S M Mansour
SM
Haeryfar
Shayan
S
Sharif
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005699:Galactosylceramides / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists* / Q000096:biosynthesis / Q000276:immunology*
D057134:Antibodies, Neutralizing; D017252:CD3 Complex; D016207:Cytokines; D005699:Galactosylceramides; D011948:Receptors, Antigen, T-Cell; D051193:Toll-Like Receptors; C493154:alpha-galactosylceramide