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In vivo activation of invariant Vα14 natural killer T cells by α‐galactosylceramide sequentially induces Fas‐dependent and ‐independent cytotoxicity
Author(s) -
Lisbonne Mariette,
Hachem Patricia,
Tonanny MarieBéatrice,
Fourneau JeanMarie,
Sidobre Stephane,
Kronenberg Mitchel,
Van Endert Peter,
Dy Michel,
Schneider Elke,
LeitedeMoraes Maria C.
Publication year - 2004
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200324828
Subject(s) - cytotoxic t cell , biology , fas ligand , cytotoxicity , natural killer t cell , microbiology and biotechnology , natural killer cell , monoclonal antibody , interleukin 21 , apoptosis , interferon gamma , interleukin 12 , immunology , cytokine , cancer research , in vitro , antibody , programmed cell death , biochemistry
Abstract The present study was designed to clarify the cytotoxic capacities of invariant Vα14 natural killer T (iNKT) cells activated in vivo . We found that as early as 2 h after a single injection of α‐galactosylceramide (α‐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 inthe 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‐γ production in α‐GalCer‐injected mice was blocked by anti‐IFN‐γ 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 α‐GalCer activation and later, through IFN‐γ secretion, enable NK cells to kill target cells in a Fas‐independent pathway.