In vivo activation of invariant V alpha 14 natural killer T cells by alpha-galactosylceramide sequentially induces Fas-dependent and -independent cytotoxicity.
The present study was designed to clarify the cytotoxic capacities of invariant V alpha 14 natural killer T (iNKT) cells activated in vivo. We found that as early as 2 h after a single injection of alpha-galactosylceramide (alpha-GalCer), sorted iNKT splenocytes from treated mice kill Fas-transfected target cells. The implication of the Fas pathway in this lysis was strengthened by both the blockage of cytotoxicity in the presence of anti-Fas ligand (FasL) monoclonal antibody (mAb) and the up-regulation of FasL expression on iNKT cells. Sorted NK cells did not participate in the lytic activity at this time point. Yet, they became cytotoxic later on, 24 h post-treatment, when target cell lysis was mainly independent of the Fas pathway. This type of cell killing was predominant at this later time point, even though iNKT cells conserved a slight Fas-dependent cytotoxicity. NK cells failed to acquire the ability to kill target cells when IFN-gamma production in alpha-GalCer-injected mice was blocked by anti-IFN-gamma mAb, underscoring the major role of this cytokine. In conclusion, our findings provide the first direct evidence that iNKT cells can exert Fas-dependent cytotoxicity very shortly after in vivo alpha-GalCer activation and later, through IFN-gamma secretion, enable NK cells to kill target cells in a Fas-independent pathway.
Lisbonne
Mariette
M
CNRS UMR 8147, Paris V, Institut de Recherche Necker Enfants Malades, Paris, France.
Hachem
Patricia
P
Tonanny
Marie-Béatrice
MB
Fourneau
Jean-Marie
JM
Sidobre
Stephane
S
Kronenberg
Mitchel
M
Van Endert
Peter
P
Dy
Michel
M
Schneider
Elke
E
Leite-de-Moraes
Maria C
MC
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D053222:Fas Ligand Protein; D005699:Galactosylceramides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D019014:fas Receptor
D000276:Adjuvants, Immunologic; D000906:Antibodies; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D005699:Galactosylceramides; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D007371:Interferon-gamma