A distinct IL-18-induced pathway to fully activate NK T lymphocytes independently from TCR engagement

MC Leite-de-Moraes, A Hameg, A Arnould… - The Journal of …, 1999 - journals.aai.org
MC Leite-de-Moraes, A Hameg, A Arnould, F Machavoine, Y Koezuka, E Schneider…
The Journal of Immunology, 1999journals.aai.org
NK T lymphocytes are characterized by their ability to promptly generate IL-4 and IFN-γ upon
TCR engagement. Here, we demonstrate that these cells can also be fully activated in the
absence of TCR cross-linking in response to the proinflammatory cytokine IL-18 associated
with IL-12. NK T cells stimulated with IL-18 plus IL-12 proliferated, killed Fas+ target cells,
and produced high levels of IFN-γ without IL-4. In these conditions, IFN-γ production was at
least 10-fold higher than that upon TCR cross-linking. Interestingly, a 2-h pretreatment with …
Abstract
NK T lymphocytes are characterized by their ability to promptly generate IL-4 and IFN-γ upon TCR engagement. Here, we demonstrate that these cells can also be fully activated in the absence of TCR cross-linking in response to the proinflammatory cytokine IL-18 associated with IL-12. NK T cells stimulated with IL-18 plus IL-12 proliferated, killed Fas+ target cells, and produced high levels of IFN-γ without IL-4. In these conditions, IFN-γ production was at least 10-fold higher than that upon TCR cross-linking. Interestingly, a 2-h pretreatment with IL-12 plus IL-18 sufficed to maintain the high IFN-γ-producing potential during subsequent stimulation with anti-TCR mAbs or with the specific Ag α-galactosylceramide. Similar effects were observed in vivo, because splenic CD4+ NK T cells from MHC class II-deficient mice secreted IFN-γ without further stimulation when removed 2 h after a single injection of IL-12 plus IL-18. In conclusion, our evidence for activation of NK T lymphocytes in response to IL-18 plus IL-12 in the absence of TCR engagement together with the maintenance of preferential IFN-γ vs IL-4 production upon subsequent exposure to specific Ags is consistent with the active participation of this cell population in innate as well as acquired cellular immune responses.
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